Novel pyridopyrazine derivatives, process of manufacturing and uses thereof

ABSTRACT

The invention relates to pyrido[2,3-b]pyrazine compounds of general formulae (Ia) and (Ib), to their preparation and use, for example, for the treatment of malignant disorders and other disorders based on pathological cell proliferations.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The invention relates to novel pyrido[2,3-b]pyrazine derivatives, toprocesses of manufacturing and use thereof, in particular as medicamentsfor the modulation of misdirected cellular signal transductionprocesses, such as modulation of tyrosine kinases, serine/threoninekinases and/or lipid kinases and for the treatment or prophylaxis ofmalignant or benign oncoses and other disorders based on pathologicalcell proliferation, for example restenosis, psoriasis, arteriosclerosisand cirrhosis of the liver.

2. Description of Related Art

The activation of protein kinases is a central event in cellular signaltransduction processes. Aberrant kinase activation is observed invarious pathological states. Targeted inhibition of kinases is thereforea fundamental therapeutic aim.

The phosphorylation of proteins is generally initiated by extracellularsignals and represents a universal mechanism for controlling variouscellular events, for example metabolic processes, cell growth, cellmigration, cell differentiation, membrane trans-port and apoptosis. Thekinase protein family is responsible for protein phosphorylation. Theseenzymes catalyse transfer of phosphate to specific substrate proteins.Based on the substrate specificity, the kinases are divided into threemain classes, tyrosine kinases, serine/threonine kinases and lipidkinases. Both receptor tyrosine kinases and cytoplasmic tyrosine,serine/threonine and lipid kinases are important proteins in cellularsignal transduction. Overexpression or overactivation of these proteinsplays an important part in disorders based on pathological cellproliferations. These include metabolic disorders, disorders of theconnective tissue and of the blood vessels, and malignant and benignoncoses. In tumor initiation and development they frequently occur asoncogens, i.e. as aberrant, constitutively active kinase proteins. Theconsequences of this excessive kinase activation are, for example,uncontrolled cell growth and reduced cell death. Stimulation oftumor-induced growth factors may also be the cause of overstimulation ofkinases. The development of kinase modulators is therefore of particularinterest for all pathogenic processes influenced by kinases.

Ras-Raf-Mek-Erk and PI3K-Akt signal transduction cascades play a centralrole in cell growth, cell proliferation, apoptosis, adhesion, migrationand glucose metabolism. Thus, the fundamental involvement in thepathogenesis of disorders such as cancer, neurodegeneration andinflammatory disorders has been demonstrated both for rasRaf-Mek-Erk andfor PI3K-Akt signaling pathway. Therefore, the individual components ofthese signal cascades constitute important therapeutic points of attackfor the intervention in the various disease processes(Weinstein-Oppenheimer C R et al., Pharmacol Ther. 2000, B8(3): 229-279,Chang F et al., Leukemia 2003, 17(3): 590-603; Chang F et al., Leukemia2003, 17(7): 1263-1293; Katso R et al., Annu Rev Cell Dev Biol. 2001,17: 615-675; and Lu Y et al., Rev Clin Exp Hematol. 2003, 7(2): 205-228;Hennessy B T et al., Nat Rev Drug Discov 2005, 4, 988-1004).

In the following, the molecular and biochemical properties of the twosignaling pathways are first described separately.

A multitude of growth factors, cytokines and oncogens transduce theirgrowth-promoting signals via the activation of G-protein-coupled ras,which leads to the activation of serine-threonine kinase Raf and to theactivation of mitogen-activated protein kinase 1 and 2 (MAPKK1/2 orMek1/2), and results in the phosphorylation and activation of MAPK 1 and2—also known as extracellular signal-regulated kinase (Erk1 and 2).Compared to other signaling pathways, ras-Raf-Mek-Erk signaling pathwaycombines a large number of proto-oncogenes, including ligands, tyrosinekinase receptors, G proteins, kinases and nuclear transcription factors.Tyrosine-kinases, for example EGFR (Mendelsohn J et al., Oncogene. 2000,19(56): 6550-6565) mediate, in the course of tumor process, caused byoverexpression and mutation, frequently constitutively active signals todownstream ras-Raf-Mek-Erk signaling pathway. Ras is mutated in 30% ofall human tumors (Khleif S N et al., J Immunother. 1999, 22(2): 155-165;Marshall C, Curr Opin Cell Biol. 1999, 11(6): 732-736) the highestincidence at 90% being in pancreas carcinomas (Friess H et al., J Mol.Med. 1996, 74(1): 35-42; Sidvatanauksorn V et al., Langenbecks ArchSurg. 1998, 383(2): 105-115). As for c-Raf, deregulated expressionand/or activation have been described in various tumors (Hoshino R etal., Oncogene 1999, 18(3): 813-822; McPhillips F et al., Br J Cancer2001, 85(11): 1753-1758). B-Raf point mutants have been detected in 66%of all human malignant melanomas, 14% of ovarian carcinomas and 12% ofcolon carcinomas (Davies H et al., Nature 2002, 417(6892): 949-954). Itis therefore not surprising that Erk1/2 is involved at primary stage inmany cellular processes, such as cell growth, cell proliferation andcell differentiation (Lewis T S et al., Adv Cancer Res. 1998, 74:49-139; Chang F et al., Leukemia 2003, 17(3): 590-603; Chang F et al.,Leukemia 2003, 17(7): 1263-1293).

In addition, members of Raf kinases also have Mek-Erk-independent,anti-apoptotic functions whose molecular steps have not yet been fullydescribed. Possible interaction partners described for theMek-Erk-independent Raf activity have been Ask1, Bcl-2, Akt and Bag1(Chen J et al., Proc Natl Acad Sci USA 2001, 98(14): 7783-7788;Troppmair J et al., Biochem Pharmacol 2003, 66(8): 1341-1345; Rapp U Ret al., Biochim Biophys Acta 2004, 1644(2-3): 149-158; Gotz R et al.,Nat Neurosci 2005, 8(9): 1169-1178). It is now assumed that bothMek-Erk-dependent and Mek-Erk-independent signal transduction mechanismscontrol the activation of upstream ras and Raf stimuli.

The isoenzymes of the phosphatidylinositol 3-kinases (PI3Ks) functionprimarily as lipid kinases and catalyse the D3 phosphorylation of secondmessenger lipids PtdIns (phosphatidylinositol) to PtdIns(3)P,PtdIns(3,4)P₂, PtdIns(3,4,5)P₃ phosphatidylinositol phosphates. PI3Ks ofclass I are composed in structural terms of catalytic subunit(p110alpha, beta, gamma, delta) and of regulatory subunit (p85alpha,beta or p101gamma). In addition, class II (PI3K-C2alpha, PI3K-C2beta)and class III (Vps34p) enzymes also belong to the family of PI3 kinases(Wymann M P et al., Biochim Biophys Acta 1998, 1436(1-2): 127-150;Vanhaesebroeck B et al., Annu Rev Biochem 2001, 70: 535-602). PIP riseinduced by PI3Ks activates proliferative ras-Raf-Mek-Erk signalingpathway via the coupling of ras (Rodriguez-Viciana P et al., Nature1994, 370(6490): 527-532) and stimulates the anti-apoptotic signalingpathway by recruiting Akt to the cell membrane and consequentlyoveractivating this kinase (Alessi D R et al., EMBO J. 1996, 15(23):6541-6551; Chang H W et al., Science 1997, 276(5320): 1848-1850; Moore SM et al., Cancer Res 1998, 58(22): 5239-5247). Thus, activation of PI3Ksfulfils at least two crucial mechanisms of tumor development,specifically activation of cell growth and cell differentiation, andinhibition of apoptosis. In addition, PI3Ks also haveprotein-phosphorylating properties (Dhand R et al., EMBO J. 1994, 13(3):522-533; Bondeva T et al., Science 1998, 282(5387): 293-296; Bondev A etal., Biol Chem 1999, 380(11): 1337-1340; Vanhaesebroeck B et al., EMBOJ. 1999, 18(5): 1292-1302), which, for example, can induce serineautophosphorylation which intrinsically regulates PI3Ks. It is alsoknown that PI3Ks have kinase-independent, regulating effectorproperties, for example in the control of heart contraction (Crackower MA et al., Cell 2002, 110(6): 737-749; Patrucco E et al., Cell. 2004,118(3): 375-387). It has also been demonstrated that PI3 Kdelta and PI3Kgamma are expressed specifically on haematopoietic cells and are thuspotential points of attack for isoenzyme-specific PI3 Kdelta and PI3Kgamma inhibitors in the treatment of inflammatory disorders, such asrheumatism, asthmas, allergies and in the treatment of B cell and T celllymphomas (Okkenhaug K et al., Nat Rev Immunol 2003, 3(4): 317-330; AliK et al., Nature 2004, 431(7011): 1007-1011; Sujobert P et al., Blood2005, 106(3): 1063-1066). PI3Kalpha, which has recently been identifiedas a proto-oncogen (Shayesteh L et al., Nat Genet. 1999, 21(1): 99-102;Ma Y Y et al., Oncogene 2000, 19(23): 2739-2744; Samuels Y et al.,Science 2004, 304(5670): 554; Campbell I G, et al., Cancer Res 2004,64(21): 7678-7681; Levine D A et al., Clin Cancer Res 2005, 11(8):2875-2878) is an important target in the therapy of tumor disorders. Thesignificance of the PI3K species as a target for active pharmaceuticalingredient (API) development is therefore extremely wide (Chang F etal., Leukemia 2003, 17(3): 590-603).

Of equally great interest are PI3K-related kinases (PIKKs), whichinclude serine/threonine kinases mTOR, ATM, ATR, h-SMG-1 and DNA-PK(Sabatini D M, Nat Rev Canc 2006, 6: 729-34; Chiang G G et al., MethodsMol Biol 2004, 281: 125-141). Their catalytic domains have a highsequence homology to the catalytic domains of PI3Ks.

Moreover, loss of tumor suppressor protein PTEN (Li J et al., Science1997, 275(5308): 1943-1947; Steck P A et al., Nat Genet. 1997, 15(4):356-362; Cully M et al., Nat Rev Canc 2006, 6: 184-192)—whose functionis the reversal of the phosphorylation initiated by PI3K—contributes tooveractivation of Akt and its downstream cascade components and henceunderlines the causal significance of PI3K as a target molecule fortumor therapy.

Various inhibitors of individual components of ras-Raf-Mek-Erk andPI3K-Akt signaling pathways have already been published and patented.

The current state of development in the field of the kinase-inhibitors,particularly of ras-Raf-Mek-Erk and of PI3K-Akt pathway, is detailed inthe reviews by J. S. Sebolt-Leopold et al., Nat Rev Cancer 2004, 4(12):937-947; R. Wetzker et al., Curr Pharm Des 2004, 10(16): 1915-1922; Z.A. Knight et al., Biochem Soc Trans. 2007, 35(Pt 2):245-9; R. A. Smithet al., Curr. Top. Med. Chem. 2006, 6, 1071-89; S. Faivre et al., NatRev Drug Discov 2006, 5, 671-688. Said publications contain acomprehensive list of published patent applications and patents whichdescribe the synthesis and use of low molecular weight ras-Raf-Mek-Erkand PI3K inhibitors.

European Commission has granted marketing authorization to Nexavar(R)(sorafenib, Bay 43-9006; WO 99/32111, WO 03/068223 in July 2006 for thetreatment of patients with advanced renal cell carcinoma who have failedprior interferon-alpha or interleukin-2 based therapy or are consideredunsuitable for such therapy. Nexavar (Bay 43-9006) exhibits a relativelyunspecific inhibition pattern of serine/threonine kinases and oftyrosine kinases, such as Raf, VEGFR2/3, Flt-3, PDGFR, c-Kit and furtherkinases. Great significance is attributed to this inhibitor in advancedtumor disorders induced by angiogenesis (for example in the case ofkidney cell carcinoma) but also in the case of melanomas with high B-Rafmutation rate. The clinical action of Bay 43-9006 is currently alsobeing determined in patients having refractory solid tumors incombination, for example, with docetaxel. To date, mild side effects andpromising anti-tumor effects have been described. Inhibition of thekinases in the PI3K-Akt signaling pathway has neither been described nordisclosed for Bay 43-9006. Recent advances in the research anddevelopment of Raf Kinase inhibitors are described in a review of R. A.Smith et al., Curr. Top. Med. Chem. 2006, 6, 1071-89.

Mek1/2 inhibitor PD0325901 (WO 02/06213) is currently in phase IIclinical trials for lung cancer and phase I/II clinical trials for thetreatment of other solid tumors. The precursor substance CI-1040 (WO00/35435, WO 00/37141) was noticeable by its high Mek specificity andtarget affinity. However, this compound was found to be metabolicallyunstable in phase I/II studies. Clinical data for the current successorsubstance PD0325901 are still to come. However, neither interaction withErk1 or Erk2 nor a function inhibiting the PI3K-Akt signaling pathway ortheir simultaneous modulation has been published or disclosed for thisMek inhibitor.

A phase II study in malignant melanoma is under way for AZD-6244(ARRY-142886), a selective MEK inhibitor from Array BioPharmaArray.

The PI3K/mTOR inhibitor BEZ-235 from Novartis (WO 06122806) entered aphase I clinical program as a targeted anticancer agent. The compoundinhibited mTOR (IC50=21 nM), p110alpha, p110alpha E542K, p110alpha H107Rand p110alpha E545K (IC50=4, 5, 18 and 4 nM, respectively) and p110beta,gamma and delta (IC50=76, 5 and 7 nM, respectively), while preservingselectivity over a panel of other kinases

Recent developments at Piramed have resulted in the synthesis of twoseries of compounds that act as phosphatidylinositol 3-kinase of classIb (PI3K-Ib) inhibitors and are described as possessing potentanticancer activity. Additional indications include immune disorders,cardiovascular diseases, metabolism/endocrine disorders,neurodegenerative diseases and bacterial or viral infections (WO06046035, WO 06046040).

Semafore recently initiated a phase I trial of its lead phosphoinositide3-kinase (PI3K) inhibitor, SF-1126 (WO 04089925), in patients with solidtumor cancers. SF-1126 is a small-molecule conjugate containing apan-PI3K inhibitor that selectively inhibits all PI3K class IA isoformsand other key members of the PI3K superfamily, including DNA PK andmTOR. Preclinically, SF-1126 has been shown to inhibit angiogenesis andcellular proliferation, induce apoptosis, block pro-survival signals andproduce synergistic antitumor effects in combination with chemotherapy.

ICOS disclosed a PI3K inhibitor IC87114 with high PI3 Kdelta isoenzymespecificity (WO 01/81346). For PI103 (WO 04/017950).

Exelixis has submitted an IND for XL-147, a novel anticancer compound.XL-147 is an orally available small-molecule inhibitor ofphosphoinositide-3 kinase (PI3K). Inactivation of PI3K has been shown toinhibit growth and induce apoptosis in tumor cells. In preclinicalstudies, XL-147 slowed tumor growth or caused tumor shrinkage inmultiple preclinical cancer models, including breast, lung, ovarian andprostate cancers, and gliomas.

Moreover, a highly noted field of research exists in the earlydevelopment of PI3K inhibitors (see reviews of Z. A. Knight et al.,Biochem Soc Trans. 2007, 35(Pt 2):245-9; R. Wetzker et al., Curr PharmDes 2004, 10(16): 1915-19222004).

Inhibitors of SAPK signaling pathway, either of Jnk or of p38, aredescribed in the literature (Gum R J et al., J Biol Chem 1998, 273(25):15605-15610; Bennett B L et al., Proc Natl Acad Sci USA. 2001, 98(24):13681-13686; Davies S P et al., Biochem J. 2000, 351(Pt 1): 95-105).However, no function of inhibiting the PI3Ks nor any specific inhibitionof Erk1 or Erk2 or else any specific inhibition of SAPKs, Erk1, Erk2, orPI3Ks has been disclosed for these SAPK inhibitors.

6- or 7-substituted pyrido[2,3-b]pyrazine derivatives find wide use inpharmaceutical chemistry as pharmacologically active compounds and assynthetic units.

Patent applications WO 04/104002 and WO 04/104003, for example, describepyrido[2,3-b]pyrazines which may be 6- or 7-substituted by urea,thiourea, amidine or guanidine groups. These compounds have propertiesas inhibitors or modulators of kinases, especially of tyrosine andserine/threonine kinases. The use as a medicament is reported. Incontrast, use of these compounds as modulators of lipid kinases, aloneor in combination with tyrosine and serine/threonine kinases, has notbeen described.

Moreover, WO 99/17759 describes pyrido[2,3-b]pyrazines which bear, in6-position, inter alia, alkyl-, aryl- and heteroaryl-substitutedcarbamates. These compounds are intended to be used for the modulationof serine-threonine protein kinase function.

Patent application WO 05/007099 describes, inter alia, urea-substitutedpyrido[2,3-b]pyrazines as inhibitors of serine/threonine kinase PKB.However, the document does not further define the R radical, whichdescribes the range of possible substitutions on urea. Therefore, therange of possible substitution on urea is thus not clearly disclosed. Asfor these compounds, use in the treatment of cancer disorders isreported. However, no specific examples of urea-substitutedpyridopyrazines having the claimed biological properties are given. Inaddition, the pyridopyrazines described here differ significantly instructure from the novel pyrido[2,3-b]pyrazines described in thisinvention.

Further examples of 6- and 7-urea-substituted pyrido[2,3-b]pyrazines arereported in WO 05/056547. However, the compounds disclosed there haveadditional carbonyl, sulphoxy, sulphone or imine substitution in the 2-or 3-position, which means that the compounds differ structurallysignificantly from the novel pyrido[2,3-b]pyrazines described in thisinvention. The pyridopyrazines reported in WO 05/056547 are described asinhibitors of protein kinases, especially of GSK-3, Syk and JAK-3. Usesreported include use in the treatment of proliferative disorders. Use ofthese compounds as modulators of lipid kinases, alone or in combinationwith serine/threonine kinases, is not described.

WO 04/005472 describes, inter alia, 6-carbamate-substitutedpyrido[2,3-b]pyrazines which, as antibacterial substances, inhibit thegrowth of bacteria. Antitumor action is not described.

Certain diphenylquinoxalines and -pyrido[2,3-b]pyrazines with specificalkylpyrrolidine, alkylpiperidine or alkylsulphonamide radicals on aphenyl ring, which may additionally also bear urea or carbamatesubstitutions in 6- or 7-position, are described in patent applicationsWO 03/084473, WO 03/086394 and WO 03/086403 as inhibitors ofserine/threonine kinase Akt. For these compounds, use in the treatmentof cancer disorders is reported. For pyrido[2,3-b]pyrazine examplecompounds described there, no defined indication of biological action isspecified. Moreover, there is a significant structural difference to thenovel pyrido[2,3-b]pyrazines described in this invention.

Moreover, patent application WO 03/024448 describes amide- andacrylamide-substituted pyrido[2,3-b]pyrazines which also containcarbamates as additional substitutents and can be used as histonedeacetylase inhibitors for the treatment of cell proliferationdisorders.

A further publication (Temple, C. Jr.; J. Med. Chem. 1990: 3044-3050)exemplarily describes the synthesis of a 6-ethyl carbamate-substitutedpyrido[2,3-b]pyrazine derivative. Antitumor action is neither disclosednor rendered obvious.

The synthesis of further derivatives of 6-ethyl carbamate-substitutedpyrido[2,3-b]pyrazine is described in a publication by R. D. Elliott(Elliott R D, J. Org. Chem. 1968: 2393-2397). Biological action of thesecompounds is neither described nor rendered obvious.

The publication by C. Temple (Temple, C. Jr., J. Med. Chem. 1968:1216-1218) describes the synthesis and examination of 6-ethylcarbamate-substituted pyrido[2,3-b]pyrazines as potential activeantimalarial ingredients. Antitumor action is neither disclosed norrendered obvious.

WO 2005/021513 is directed to the preparation of condensedn-pyrazinyl-sulfonamides and their use in the treatment of chemokinemediated diseases. Antitumor action is neither disclosed nor renderedobvious.

JP 2006137723 describes the preparation of sulfonamides, their use asCCL17 and/or 22 regulators, and pharmaceuticals containing them fortreatment of the chemokine-associated diseases. Antitumor action isneither disclosed nor rendered obvious.

Sako M. (Sako M., Houben-Weyl, Science of Synthesis 2004, 16.20:1269-1290) gives a general overview about the synthesis ofpyridopyrazines. Antitumor action is neither disclosed nor renderedobvious.

U.S. Pat. No. 4,082,845 discloses3-(1-piperazinyl)-pyrido[2,3-b]pyrazines. Antitumor action is neitherdisclosed nor rendered obvious.

WO 04/005472 relates to antibacterial inhibitors of Ftsz protein.Pyridopyrazines are not explicitly mentioned. Antitumor action isneither disclosed nor rendered obvious.

WO 02/090355 describes the preparation of N-aroyl cyclic amines asorexin antagonists. Pyrido[2,3-b]pyrazines are not mentioned.

JP 50053394 discloses 3-substituted5-alkyl-5,8-dihydro-8-oxopyrido[2,3-b]pyrazine-7-carboxylic acids andtheir esters. Antitumor action is neither disclosed nor renderedobvious.

U.S. Pat. No. 3,209,004 relates to3,6-diamino-N-(2,2-dialkoxyethyl)pyrido[2,3-b]pyrazine-2-carboxamides.Antitumor action is neither disclosed nor rendered obvious.

U.S. Pat. No. 3,180,868 describes3,6-diamino-N-(substituted)pyrido[2,3-b]pyrazine-2-carboxamides.Antitumor action is neither disclosed nor rendered obvious.

Chen J J et al. (Chen J J et al., J. Am. Chem. Soc. 1996, 118:8953-8954) discuss the synthesis of pyrido[2,3-b]pyrazines from pyrazineC-nucleosides. Antitumor action is neither disclosed nor renderedobvious.

Nagel A et al. (Nagel A et al., J. Heterocyclic Chem. 1979, 16: 301-304)show NMR data of pyrido[2,3-b]pyrazine derivatives. Antitumor action isneither disclosed nor rendered obvious.

Tanaka T et al. (Tanaka T et al., Yakugaku Zasshi 1975, 95(9):1092-1097) describe the synthesis of certain pyrido[2,3-b]pyrazinederivatives. Antitumor action is neither disclosed nor rendered obvious.

Osdene T S et al. (Osdene T S et al., J. Chem. Soc. 1955, pp. 2032-2035)discuss the synthesis of 3,6-diaminopyridopyrazine and derived compoundswith potential anti-folic acid activity. Antitumor action is neitherdisclosed nor rendered obvious.

WO 2006/128172 is directed to a method for treating B cell regulatedautoimmune disorders. Pyrido[2,3-b]pyrazines are not disclosed.Antitumor action is neither disclosed nor rendered obvious.

WO 2006/091395 relates to inhibitors of serine/threonine kinase Aktactivity. Pyrido[2,3-b]pyrazine derivatives are comprised. However,possible pyrido[2,3-b]pyrazine derivatives are substituted withsubstituted phenyl and (C₃-C₈)cycloalkyl, aryl, heteroaryl andheterocyclyl.

WO 06/081179, WO 06/017326, WO 06/017468, WO 06/014580, WO 06/012396, WO06/002047 and WO 06/020561 are all directed to antibacterial agents.Pyrido[2,3-b]pyrazines are not disclosed. Antitumor action is neitherdisclosed nor rendered obvious.

WO 2006/074147 discloses 4-arylamino-quinazolines as activatots ofcaspases and inducers of apoptosis. Pyrido[2,3-b]pyrazines are notdisclosed. Antitumor action is neither disclosed nor rendered obvious.

WO 2006/024666 relates to the preparation of pyridine methylenethioxothiazolidinones as phosphoinositide inhibitors.Pyrido[2,3-b]pyrazine derivatives are comprised. However, the displayedpyrido[2,3-b]pyrazine derivatives are not substituted at their pyrazinemoiety.

WO 06/021448 is directed to compounds with antibacterial action.Pyrido[2,3-b]pyrazines are not disclosed. Antitumor action is neitherdisclosed nor rendered obvious.

WO 2005/123733 describes pyrido[2,3-b]pyrazine derivatives as agents forcombatting phytopathogenic fungi. However, possiblepyrido[2,3-b]pyrazine derivatives are substituted with aryl, heteraryl,halogen or substituted amino at their pyridine moiety.

WO 2005/123698 describes agents for combatting phytopathogenic fungi.Pyrido[2,3-b]pyrazine derivatives are comprised. However, the comprisedpyrido[2,3-b]pyrazine derivatives are substituted with aryl, heteraryl,halogen or substituted amino at their pyridine moiety.

US 2005/0272736 relates to tri-and bi-cyclic heteroaryl histamine-3receptor ligands. Pyrido[2,3-b]pyrazines are not disclosed. Antitumoraction is neither disclosed nor rendered obvious.

US 2005/0272728 discloses bicyclic amines bearing heterocyclicsubstituents as H3 receptor ligands. Pyrido[2,3-b]pyrazines are notdisclosed. Antitumor action is neither disclosed nor rendered obvious.

US 2005/0256309 relates to tri-and bi-cyclic heteroaryl histamine-3receptor ligands. Pyrido[2,3-b]pyrazines are not disclosed. Antitumoraction is neither disclosed nor rendered obvious.

US 2005/0256118 discloses bicyclic amines bearing heterocyclicsubstituents as H3 receptor ligands. Pyrido[2,3-b]pyrazines are notdisclosed. Antitumor action is neither disclosed nor rendered obvious.

US 2005/0165028 is directed to N-heteroaryl substituted benzamides asvanilloid receptor ligands. Pyrido[2,3-b]pyrazines are not disclosed.Antitumor action is neither disclosed nor rendered obvious.

WO 05/023807 describes bicyclic quinazolin-4-ylamine derivatives ascapsaicin receptor modulators. Pyrido[2,3-b]pyrazines are not disclosed.Antitumor action is neither disclosed nor rendered obvious.

EP 1 661 889, which corresponds to WO 2005/07099, relates to pyridinylbenzene-sulfonylamide derivatives as chemokine receptor antagonist.Pyrido[2,3-b]pyrazine derivatives are comprised. However, the comprisedpyrido[2,3-b]pyrazine derivatives are concomitantly substituted withsulfonamides and cyclic structures.

WO 04/055003 discloses quinazolin-4-yl)amines as capsaicin receptormodulators. Pyrido[2,3-b]pyrazines are not disclosed. Antitumor actionis neither disclosed nor rendered obvious.

US 2004/0092521 discloses bicyclic amines bearing heterocyclicsubstituents as H3 receptor ligands. Pyrido[2,3-b]pyrazines are notdisclosed. Antitumor action is neither disclosed nor rendered obvious.

WO 2004/030635 is directed to vasculostatic agents.Pyrido[2,3-b]pyrazine derivatives are comprised. However, the comprisedpyrido[2,3-b]pyrazine derivatives are substituted with aryl or heterarylat their pyrazine moiety.

WO 03/064421 describes aminopiperidine derivatives as antibacterialagents. Pyrido[2,3-b]pyrazines are not disclosed. Antitumor action isneither disclosed nor rendered obvious.

WO 03/064431 also describes aminopiperidine derivatives as antibacterialagents. Pyrido[2,3-b]pyrazines are not disclosed. Antitumor action isneither disclosed nor rendered obvious.

WO 02/055079 relates to 8-hydroxy-1,6-naphthyridine-7-carboxamides asinhibitors of HIV integrase and HIV replication. Pyrido[2,3-b]pyrazinesare not disclosed. Antitumor action is neither disclosed nor renderedobvious.

WO 00/12497 discloses quinazoline derivatives as TGF-beta and p38-alphakinase inhibitors. However, pyrido[2,3-b]pyrazines are not disclosed.

WO 99/43681 is directed toN-(4-piperidinylmethyl)thieno[3,2-b]pyridin-7-amines and relatedcompounds as GABA brain receptor ligands. Pyrido[2,3-b]pyrazines are notdisclosed. Antitumor action is neither disclosed nor rendered obvious.

WO 95/15758 describes aryl and heteroaryl quinazoline compounds whichinhibit CSF-1R receptor tyrosine kinase. Pyrido[2,3-b]pyrazines are notdisclosed.

U.S. Pat. No. 5,480,883 describes bis mono- and bicyclic aryl andheteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosinekinase. Pyrido[2,3-b]pyrazine derivatives are comprised. However, thecomprised pyrido[2,3-b]pyrazine derivatives are directly substitutedwith aryl or heteraryl at their pyrazine moiety.

WO 2006/059103 relates to substituted pyridines and derivatives thereof.Pyrido[2,3-b]pyrazines are not disclosed.

WO 2007/023186 discloses pyrazine derivatives and their use as PI3Kinhibitors. Pyrido[2,3-b]pyrazine derivatives are comprised. However,the comprised pyrido[2,3-b]pyrazine derivatives are directly substitutedwith sulfonamides at their pyrazine moiety.

WO 2007/044729 also describes pyrazine derivatives and their use as PI3Kinhibitors. Pyrido[2,3-b]pyrazine derivatives are comprised. However,the comprised pyrido[2,3-b]pyrazine derivatives are directly substitutedwith sulfonamides at their pyrazine moiety.

WO 2004/108702 is directed to indole derivatives. Pyrido[2,3-b]pyrazinederivatives are comprised. However, the comprised pyrido[2,3-b]pyrazinederivatives are directly substituted with glyoxyl-indolyl at theirpyrimidine moiety.

DESCRIPTION OF THE INVENTION

The present invention has the object to provide novelpyrido[2,3-b]pyrazine derivatives that act as kinase modulators.

The object of the present invention has surprisingly been solved in oneaspect by providing pyrido[2,3-b]pyrazine derivatives according togeneral formula (Ia)

wherein:one of radicals R3, R4 independently is selected, or both of radicalsR3, R4 independently from each other are selected from the groupconsisting of:

-   (1) “—NR6R7”;    wherein radicals R6, R7 are independently from each other selected    from the group consisting of:    (a) “hydrogen, alkyl, arylalkyl, heteroarylalkyl”;    -   with the first proviso that radicals R6, R7 are not both        hydrogen, alkyl, arylalkyl or heteroarylalkyl at the same time;    -   with the second proviso that, if one of radicals R6, R7        independently is “hydrogen”, radical R5 is not selected from the        group consisting of: “—NH-cycloalkyl, —NH-heterocyclyl,        —NH-aryl, —NH-heteroaryl, halogen, —F, —Cl, —Br, —I,        —NR_(a)R_(b)”, with Ra, Rb being independently selected from the        group consisting of: “H, alkyl, cycloalkyl, cycloalkylalkyl,        aryl, arylalkyl, heteroaryl, heteroarylalkyl, —NR_(c)R_(d)”, Rc,        Rd in turn being independently selected from the group        consisting of: “H, alkyl, cycloalkyl, cycloalkylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl”;        (b) “—C(Y1)NR8R9, —C(Y1b)OR9b, —C(═NR10)-R11,        —C(Y2)NR12-Y3-R13”;    -   wherein Y1, Y1b, Y2 are independently from each other selected        from the group consisting of: “═O, ═S, ═NH, ═NR14”;    -   wherein Y3 is independently selected from the group consisting        of: “O, S”;    -   wherein radicals R8, R9, R9b, R10, R11, R12, R13, R14 are        independently from each other selected from the group consisting        of:    -   (I) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, —F, —Cl, —Br, —I, —CN,        —CF₃, —N₃, —NH₂, —NHX1, —NX2×3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH,        —O—SO₃H, —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, SO₃H, —P(O)(OH)₂,        —C(O)—X4, —C(O)O—X5, —C(O)NH—X6, —C(O)NX7X8, —O—X9,        —O(—X10-O)_(a)—H (a=1, 2, 3, 4, 5), —O(—X11-O)_(b)—X12 (b=1, 2,        3, 4, 5), —OC(O)—X13, —OC(O)—O—X14, —OC(O)—NHX15,        —O—C(O)—NX16×17, —OP(O)(OX18)(OX19), —OSi(X20)(X21)(X22),        —OS(O₂)—X23, —NHC(O)—NH₂, —NHC(O)—X24, —NX25C(O)—X26,        —NH—C(O)—O—X27, —NH—C(O)—NH—X28, —NH—C(O)—NX29×30,        —NX31-C(O)—O—X32, —NX33-C(O)—NH—X34, —NX35-C(O)—NX36×37,        —NHS(O₂)—X38, —NX39S(O₂)—X40, —S—X41, —S(O)—X42, —S(O₂)—X43,        —S(O₂)NH—X44, —S(O₂)NX45×46, —S(O₂)O—X47, —P(O)(OX48)(OX49),        —Si(X50)(X51)(X52), —C(NH)—NH₂, —C(NX53)-NH₂, —C(NH)—NHX54,        —C(NH)—NX55×56, —C(NX57)-NHX58, —C(NX59)-NX60×61,        —NH—C(O)—NH—O—X62, —NH—C(O)—NX63-O—X64, —NX65-C(O)—NX66-O—X67,        —N(—C(O)—NH—O—X68)₂, —N(—C(O)—NX69-O—X70)₂,        —N(—C(O)—NH—O—X71)(—C(O)—NX72-O—X73), —C(S)—X74, —C(S)—O—X75,        —C(S)—NH—X76, —C(S)—NX77×78, —C(O)—NH—O—X79, —C(O)—NX80-O—X81,        —C(S)—NH—O—X82, —C(S)—NX83-O—X84, —C(O)—NH—NH—X85,        —C(O)—NH—NX86×87, —C(O)—NX88-NX89×90, —C(S)—NH—NH—X91,        —C(S)—NH—NX92×93, —C(S)—NX94-NX95×96, —C(O)—C(O)—O—X97,        —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX98, —C(O)—C(O)—NX99×100,        —C(S)—C(O)—O—X101, —C(O)—C(S)—O—X102, —C(S)—C(S)—O—X103,        —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX104, —C(S)—C(O)—NX105X106,        —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX107, —C(S)—C(S)—NX108X10⁹,        —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX110, —C(O)—C(S)—NX111X112”;        -   wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12,            X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24,            X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36,            X37, X38, X39, X40, X41, X42, X43, X44, X45, X46, X47, X48,            X49, X50, X51, X52, X53, X54, X55, X56, X57, X58, X59, X60,            X61, X62, X63, X64, X65, X66, X67, X68, X69, X70, X71, X72,            X73, X74, X75, X76, X77, X78, X79, X80, X81, X82, X83, X84,            X85, X86, X87, X88, X89, X90, X91, X92, X93, X94, X95, X96,            X97, X98, X99, X100, X101, X102, X103, X104, X105, X106,            X107, X108, X109, X110, X111, X112 are independently from            each other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and wherein alternatively X7,            X8 and/or X16, X17 and/or X29, X30 and/or X36, X37 and/or            X45, X46 and/or X55, X56 and/or X60, X61 and/or X77, X78            and/or X86, X87 and/or X89, X90 and/or X92, X93 and/or X95,            X96 and/or X99, X100 and/or X105, X106 and/or X108, X109            and/or X111, X112 and/or respectively together can also form            “heterocyclyl”;        -   wherein optionally above substituents of substituents group            (I)—if not hydrogen—can in turn independently from each            other be substituted with at least one substituent,            identical or different, selected from the group consisting            of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHX201, —NX202×203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X204, —C(O)O—X205, —C(O)NH—X206, —C(O)NX207×208, —O—X209,        —O(—X210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(—X211-O)_(d)—X212 (d=1,        2, 3, 4, 5), —OC(O)—X213, —OC(O)—O—X214, —OC(O)—NHX215,        —O—C(O)—NX216×217, —OP(O)(OX218)(OX219), —OSi(X220)(X221)(X222),        —OS(O₂)—X223, —NHC(O)—NH₂, —NHC(O)—X224, —NX225C(O)—X226,        —NH—C(O)—O—X227, —NH—C(O)—NH—X228, —NH—C(O)—NX229×230,        —NX231-C(O)—O—X232, —NX233-C(O)—NH—X234, —NX235-C(O)—NX236×237,        —NHS(O₂)—X238, —NX239S(O₂)—X240, —S—X241, —S(O)—X242,        —S(O₂)—X243, —S(O₂)NH—X244, —S(O₂)NX245×246, —S(O₂)O—X247,        —P(O)(OX248)(OX249), —Si(X250)(X251)(X252), —C(NH)—NH₂,        —C(NX253)-NH₂, —C(NH)—NHX254, —C(NH)—NX255×256,        —C(NX257)-NHX258, —C(NX259)-NX260×261, —NH—C(O)—NH—O—X262,        —NH—C(O)—NX263-O—X264, —NX265-C(O)—NX266-O—X267,        —N(—C(O)—NH—O—X268)₂, —N(—C(O)—NX269-O—X270)₂,        —N(—C(O)—NH—O—X271)(—C(O)—NX272-O—X273), —C(S)—X274,        —C(S)—O—X275, —C(S)—NH—X276, —C(S)—NX277×278, —C(O)—NH—O—X279,        —C(O)—NX280-O—X281, —C(S)—NH—O—X282, —C(S)—NX283-O—X284,        —C(O)—NH—NH—X285, —C(O)—NH—NX286×287, —C(O)—NX288-NX289×290,        —C(S)—NH—NH—X291, —C(S)—NH—NX292×293, —C(S—NX294-NX295×296,        —C(O)—C(O)—O—X297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX298,        —C(O)—C(O)—NX299×300, —C(S)—C(O)—O—X301, —C(O)—C(S)—O—X302,        —C(S)—C(S)—O—X303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX304,        —C(S)—C(O)—NX305×306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX307,        —C(S)—C(S)—NX308×309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX310,        —C(O)—C(S)—NX311×312”;        -   wherein X201, X202, X203, X204, X205, X206, X207, X208,            X209, X210, X211, X212, X213, X214, X215, X216, X217, X218,            X219, X220, X221, X222, X223, X224, X225, X226, X227, X228,            X229, X230, X231, X232, X233, X234, X235, X236, X237, X238,            X239, X240, X241, X242, X243, X244, X245, X246, X247, X248,            X249, X250, X251, X252, X253, X254, X255, X256, X257, X258,            X259, X260, X261, X262, X263, X264, X265, X266, X267, X268,            X269, X270, X271, X272, X273, X274, X275, X276, X277, X278,            X279, X280, X281, X282, X283, X284, X285, X286, X287, X288,            X289, X290, X291, X292, X293, X294, X295, X296, X297, X298,            X299, X300, X301, X302, X303, X304, X305, X306, X307, X308,            X309, X310, X311, X312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively X207, X208 and/or            X216, X217 and/or X229, X230 and/or X236, X237 and/or X245,            X246 and/or X255, X256 and/or X260, X261 and/or X277, X278            and/or X286, X287 and/or X289, X290 and/or X292, X293 and/or            X295, X296 and/or X299, X300 and/or X305, X306 and/or X308,            X309 and/or X311, X312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHX401, —NX402×403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X404, —C(O)O—X405, —C(O)NH—X406, —C(O)NX407×408, —O—X409,        —O(—X410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—X411-O)_(f)—X412 (f=1,        2, 3, 4, 5), —OC(O)—X413, —OC(O)—O—X414, —OC(O)—NHX415,        —O—C(O)—NX416×417, —OP(O)(OX418)(OX419), —OSi(X420)(X421)(X422),        —OS(O₂)—X423, —NHC(O)—NH₂, —NHC(O)—X424, —NX425C(O)—X426,        —NH—C(O)—O—X427, —NH—C(O)—NH—X428, —NH—C(O)—NX429×430,        —NX431-C(O)—O—X432, —NX433-C(O)—NH—X434, —NX435-C(O)—NX436×437,        —NHS(O₂)—X438, —NX439S(O₂)—X440, —S—X441, —S(O)—X442,        —S(O₂)—X443, —S(O₂)NH—X444, —S(O₂)NX445×446, —S(O₂)O—X447,        —P(O)(OX448)(OX449), —Si(X450)(X451)(X452), —C(NH)—NH₂,        —C(NX453)-NH₂, —C(NH)—NHX454, —C(NH)—NX455×456,        —C(NX457)-NHX458, —C(NX459)-NX460×461, —NH—C(O)—NH—O—X462,        —NH—C(O)—NX463-O—X464, —NX465-C(O)—NX466-O—X467,        —N(—C(O)—NH—O—X468)₂, —N(—C(O)—NX469-O—X470)₂,        —N(—C(O)—NH—O—X471) (—C(O)—NX472-O—X473), —C(S)—X474,        —C(S)—O—X475, —C(S)—NH—X476, —C(S)—NX477×478, —C(O)—NH—O—X479,        —C(O)—NX480-O—X481, —C(S)—NH—O—X482, —C(S)—NX483-O—X484,        —C(O)—NH—NH—X485, —C(O)—NH—NX486×487, —C(O)—NX488-NX489×490,        —C(S)—NH—NH—X491, —C(S)—NH—NX492×493, —C(S)—NX494-NX495×496,        —C(O)—C(O)—O—X497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX498,        —C(O)—C(O)—NX499×500, —C(S)—C(O)—O—X501, —C(O)—C(S)—O—X502,        —C(S)—C(S)—O—X503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX504,        —C(S)—C(O)—NX505×506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX507,        —C(S)—C(S)—NX508×509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX510,        —C(O)—C(S)—NX511×512”;        -   wherein X401, X402, X403, X404, X405, X406, X407, X408,            X409, X410, X411, X412, X413, X414, X415, X416, X417, X418,            X419, X420, X421, X422, X423, X424, X425, X426, X427, X428,            X429, X430, X431, X432, X433, X434, X435, X436, X437, X438,            X439, X440, X441, X442, X443, X444, X445, X446, X447, X448,            X449, X450, X451, X452, X453, X454, X455, X456, X457, X458,            X459, X460, X461, X462, X463, X464, X465, X466, X467, X468,            X469, X470, X471, X472, X473, X474, X475, X476, X477, X478,            X479, X480, X481, X482, X483, X484, X485, X486, X487, X488,            X489, X490, X491, X492, X493, X494, X495, X496, X497, X498,            X499, X500, X501, X502, X503, X504, X505, X506, X507, X508,            X509, X510, X511, X512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively X407, X408 and/or            X416, X417 and/or X429, X430 and/or X436, X437 and/or X445,            X446 and/or X455, X456 and/or X460, X461 and/or X477, X478            and/or X486, X487 and/or X489, X490 and/or X492, X493 and/or            X495, X496 and/or X499, X500 and/or X505, X506 and/or X508,            X509 and/or X511, X512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHX601, —NX602×603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X604, —C(O)O—X605, —C(O)NH—X606, —C(O)NX607×608, —O—X609,        —O(—X610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—X611-O)_(f)—X612 (f=1,        2, 3, 4, 5), —OC(O)—X613, —OC(O)—O—X614, —OC(O)—NHX615,        —O—C(O)—NX616×617, —OP(O)(OX618)(OX619), —OSi(X620)(X621)(X622),        —OS(O₂)—X623, —NHC(O)—NH₂, —NHC(O)—X624, —NX625C(O)—X626,        —NH—C(O)—O—X627, —NH—C(O)—NH—X628, —NH—C(O)—NX629×630,        —NX631-C(O)—O—X632, —NX633-C(O)—NH—X634, —NX635-C(O)—NX636×637,        —NHS(O₂)—X638, —NX639S(O₂)—X640, —S—X641, —S(O)—X642,        —S(O₂)—X643, —S(O₂)NH—X644, —S(O₂)NX645×646, —S(O₂)O—X647,        —P(O)(OX648)(OX649), —Si(X650)(X651)(X652), —C(NH)—NH₂,        —C(NX653)-NH₂, —C(NH)—NHX654, —C(NH)—NX655×656,        —C(NX657)-NHX658, —C(NX659)-NX660×661, —NH—C(O)—NH—O—X662,        —NH—C(O)—NX663-O—X664, —NX665-C(O)—NX666-O—X667,        —N(—C(O)—NH—O—X668)₂, —N(—C(O)—NX669-O—X670)₂,        —N(—O(O)—NH—O—X671)(—C(O)—NX672-O—X673), —C(S)—X674,        —C(S)—O—X675, —C(S)—NH—X676, —C(S)—NX677×678, —C(O)—NH—O—X679,        —C(O)—NX680-O—X681, —C(S)—NH—O—X682, —C(S)—NX683-O—X684,        —C(O)—NH—NH—X685, —C(O)—NH—NX686×687, —C(O)—NX688-NX689×690,        —C(S)—NH—NH—X691, —C(S)—NH—NX692×693, —C(S)—NX694-NX695×696,        —C(O)—C(O)—O—X697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX698,        —C(O)—C(O)—NX699×700, —C(S)—C(O)—O—X701, —C(O)—C(S)—O—X702,        —C(S)—C(S)—O—X703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX704,        —C(S)—C(O)—NX705×706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX707,        —C(S)—C(S)—C(S)—NX711×712”;        -   wherein X601, X602, X603, X604, X605, X606, X607, X608,            X609, X610, X611, X612, X613, X614, X615, X616, X617, X618,            X619, X620, X621, X622, X623, X624, X625, X626, X627, X628,            X629, X630, X631, X632, X633, X634, X635, X636, X637, X638,            X639, X640, X641, X642, X643, X644, X645, X646, X647, X648,            X649, X650, X651, X652, X653, X654, X655, X656, X657, X658,            X659, X660, X661, X662, X663, X664, X665, X666, X667, X668,            X669, X670, X671, X672, X673, X674, X675, X676, X677, X678,            X679, X680, X681, X682, X683, X684, X685, X686, X687, X688,            X689, X690, X691, X692, X693, X694, X695, X696, X697, X698,            X699, X700, X701, X702, X703, X704, X705, X706, X707, X708,            X709, X710, X711, X712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively X607, X608 and/or            X616, X617 and/or X629, X630 and/or X636, X637 and/or X645,            X646 and/or X655, X656 and/or X660, X661 and/or X677, X678            and/or X686, X687 and/or X689, X690 and/or X692, X693 and/or            X695, X696 and/or X699, X700 and/or X705, X706 and/or X708,            X709 and/or X711, X712 and/or respectively together can also            form “heterocyclyl”;    -   with the first proviso that if “—C(Y1)-NR₈R₉” is selected from        the group consisting of: “—C(O)—NR_(a)R_(b)”, with Ra, Rb        independently from each other being selected from the group        consisting of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, aryl, arylalkyl,        heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl” or with Ra, Rb forming together        “heterocyclyl”, one of radicals R1, R2 is not “hydrogen” and the        other one of radicals R1, R2 is not “—NR_(c)R_(d) with Rc, Rd        independently from each other being selected from the group        consisting of: “hydrogen, alkyl, (C₉-C₃₀alkyl), cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, —C(Ya1)NXa16Xa17,        —C(═NXa18)-Xa19, —C(Ya2)NXa20-Ya3-Xa21”; with the proviso that        Rc, Rd are not “hydrogen” or “alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl” at the same time, with        the further proviso that if one of radicals Rc, Rd is “hydrogen”        or “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl”, the other radical Rc, Rd is        “—C(Ya1)NXa16Xa17”, “—C(═NXa18)-Xa19” oder        “—C(Ya2)NXa20-Ya3-Xa21”, where Ya1, Ya2, Ya3 are independently        from each other selected from the group consisting of “O, S,        ═NH, ═NXa22”; where Xa16, Xa17, Xa18, Xa19, Xa20, Z21, Z22 are        independently from each other selected from the group consisting        of: hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        aryl, arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,        heterocyclylalkyl”;    -   with the second proviso that if at least one of radicals R1, R2        is “-NXa26Xa27” with at least one of radicals Xa26, Xa27 being        “—C(O)—NR_(e)R_(f) where at least one of radicals R_(e), R_(f)        is selected from the group consisting of: “alkyl, cycloalkyl,        heterocyclyl, aryl, heteroaryl, C(O)-alkyl, C(O)-aryl,        C(O)-heteroaryl, (C₉-C₃₀)alkyl, cycloalkylalkyl,        heterocyclylalkyl, arylalkyl, heteroarylalkyl,        —C(O)—(C₉-C₃₀)alkyl, —C(O)-cycloalkyl, —C(O)-cycloalkylalkyl,        —C(O)-arylalkyl, —C(O)heteroarylalkyl, —C(O)-heterocyclyl,        —C(O)-heterocyclylalkyl, —S(O₂)-alkyl, —S(O₂)—(C₉-C₃₀)alkyl,        —S(O₂)-cycloalkyl, —S(O₂)-cycloalkylalkyl, —S(O₂)-aryl,        —S(O₂)-arylalkyl, —S(O₂)-heteroaryl, —S(O₂)-heteroarylalkyl,        —S(O₂)— heterocyclyl, —S(O₂)-heterocyclylalkyl”, radicals R3, R4        are not “—C(O)—NXa1135Xa1136 with Xa1135, Xa1136 independently        being selected from the group consisting of: hydrogen, alkyl,        (C₉-C₃₀alkyl), cycloalkyl, cycloalkylalkyl, heterocyclyl,        heterocyclylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl”        or with Xa1135, Xa1136 forming together “heterocyclyl”;    -   with the third proviso that, if “—C(Y1)-NR8R9” independently is        selected from the group consisting of: “—C(O)—N[C(O)—O-alkyl]₂,        —C(O)—N[C(O)-alkyl]₂, —C(O)—N[S(O₂)-alkyl]₂,        —C(O)—N[S(O₂)-cycloalkyl]₂, —C(O)—N[S(O₂)—cycloalkylalkyl]₂,        —C(O)—N[S(O₂)-aryl]₂, —C(O)—N[S(O₂)-heterocyclyl]₂”, radicals        R1, R2 independently from each other are not “phenyl”;    -   with the fourth proviso that, if “—C(Y2)-NR12-Y3-R13”        independently is selected from the group consisting of:        “—C(O)—N[O-alkyl]₂”, radicals R1, R2 independently from each        other are not “phenyl”;

(c) “—C(O)—C(O)—R16”;

-   -   wherein radical R16 is independently selected from the group        consisting of:    -   (II) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, —F, —Cl, —Br, —I, —CN,        —CF₃, —N₃, —NH₂, —NHZ1, —NZ2Z3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH,        —O—SO₃H, —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z4, —C(O)O—Z5, —C(O)NH—Z6, —C(O)NZ7Z8, —O—Z9,        —O(—Z10-O)_(a)—H (a=1, 2, 3, 4, 5), —O(—Z11-O)_(b)—Z12 (b=1, 2,        3, 4, 5), —OC(O)—Z13, —OC(O)—O—Z14, —OC(O)—NHZ15,        —O—C(O)—NZ16Z17, —OP(O)(OZ18)(OZ19), —OSi(Z20)(Z21)(Z22),        —OS(O₂)—Z23, —NHC(O)—NH₂, —NHC(O)—Z24, —NZ25C(O)—Z26,        —NH—C(O)—O—Z27, —NH—C(O)—NH—Z28, —NH—C(O)—NZ29Z30,        —NZ31-C(O)—O—Z32, —NZ33-C(O)—NH—Z34, —NZ35-C(O)—NZ36Z37,        —NHS(O₂)—Z38, —NZ39S(O₂)—Z40, —S—Z41, —S(O)—Z42, —S(O₂)—Z43,        —S(O₂)NH—Z44, —S(O₂)NZ45Z46, —S(O₂)O—Z47, —P(O)(OZ48)(OZ49),        —Si(Z50)(Z51)(Z52), —C(NH)—NH₂, —C(NZ53)-NH₂, —C(NH)—NHZ54,        —C(NH)—NZ55Z56, —C(NZ57)-NHZ58, —C(NZ59)-NZ60Z61,        —NH—C(O)—NH—O—Z62, —NH—C(O)—NZ63-O—Z64, —NZ65-C(O)—NZ66-O—Z67,        —N(—C(O)—NH—O—Z68)₂, —N(—C(O)—NZ69-O—Z70)₂,        —N(—C(O)—NH—O—Z71)(—C(O)—NZ72-O—Z73), —C(S)—Z74, —C(S)—O—Z75,        —C(S)—NH—Z76, —C(S)—NZ77Z78, —C(O)—NH—O—Z79, —C(O)—NZ80-O—Z81,        —C(S)—NH—O—Z82, —C(S)—NZ83-O—Z84, —C(O)—NH—NH—Z85,        —C(O)—NH—NZ86Z87, —C(O)—NZ88-NZ89Z90, —C(S)—NH—NH—Z91,        —C(S)—NH—NZ92Z93, —C(S)—NZ94-NZ95Z96, —C(O)—C(O)—O—Z97,        —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ98, —C(O)—C(O)—NZ99Z100,        —C(S)—C(O)—O—Z101, —C(O)—C(S)—O—Z102, —C(S)—C(S)—O—Z103,        —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ104, —C(S)—C(O)—NZ105Z106,        —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ107, —C(S)—C(S)—NZ108Z109,        —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ110, —C(O)—C(S)—NZ111Z112”;        -   wherein Z1, Z2, Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12,            Z13, Z14, Z15, Z16, Z17, Z18, Z19, Z20, Z21, Z22, Z23, Z24,            Z25, Z26, Z27, Z28, Z29, Z30, Z31, Z32, Z33, Z34, Z35, Z36,            Z37, Z38, Z39, Z40, Z41, Z42, Z43, Z44, Z45, Z46, Z47, Z48,            Z49, Z50, Z51, Z52, Z53, Z54, Z55, Z56, Z57, Z58, Z59, Z60,            Z61, Z62, Z63, Z64, Z65, Z66, Z67, Z68, Z69, Z70, Z71, Z72,            Z73, Z74, Z75, Z76, Z77, Z78, Z79, Z80, Z81, Z82, Z83, Z84,            Z85, Z86, Z87, Z88, Z89, Z90, Z91, Z92, Z93, Z94, Z95, Z96,            Z97, Z98, Z99, Z100, Z101, Z102, Z103, Z104, Z105, Z106,            Z107, Z108, Z109, Z110, Z111, Z112 are independently from            each other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and        -   wherein alternatively Z7, Z8 and/or Z16, Z17 and/or Z29, Z30            and/or Z36, Z37 and/or Z45, Z46 and/or Z55, Z56 and/or Z60,            Z61 and/or Z77, Z78 and/or Z86, Z87 and/or Z89, Z90 and/or            Z92, Z93 and/or Z95, Z96 and/or Z99, Z100 and/or Z105, Z106            and/or Z108, Z109 and/or Z111, Z112 and/or respectively            together can also form “heterocyclyl”;        -   wherein optionally above substituents of substituents group            (II)—if not hydrogen—can in turn independently from each            other be substituted with at least one substituent,            identical or different, selected from the group consisting            of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHZ201, —NZ202Z203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z204, —C(O)O—Z205, —C(O)NH—Z206, —C(O)NZ207Z208, —O—Z209,        —O(—Z210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(—Z211-O)_(d)—Z212 (d=1,        2, 3, 4, 5), —OC(O)—Z213, —OC(O)—O—Z214, —OC(O)—NHZ215,        —O—C(O)—NZ216Z217, —OP(O)(OZ218)(OZ219), —OSi(Z220)(Z221)(Z222),        —OS(O₂)—Z223, —NHC(O)—NH₂, —NHC(O)—Z224, —NZ225C(O)—Z226,        —NH—C(O)—O—Z227, —NH—C(O)—NH—Z228, —NH—C(O)—NZ229Z230,        —NZ231-C(O)—O—Z232, —NZ233-C(O)—NH—Z234, —NZ235-C(O)—NZ236Z237,        —NHS(O₂)—Z238, —NZ239S(O₂)— Z240, —S—Z241, —S(O)—Z242,        —S(O₂)—Z243, —S(O₂)NH—Z244, —S(O₂)NZ245Z246, —S(O₂)O—Z247,        —P(O)(OZ248)(OZ249), —Si(Z250)(Z251)(Z252), —C(NH)—NH₂,        —C(NZ253)-NH₂, —C(NH)—NHZ254, —C(NH)—NZ255Z256,        —C(NZ257)-NHZ258, —C(NZ259)-NZ260Z261, —NH—C(O)—NH—O—Z262,        —NH—C(O)—NZ263-O—Z264, —NZ265-C(O)—NZ266-O—Z267,        —N(—C(O)—NH—O—Z268)₂, —N(—C(O)—NZ269-O—Z270)₂,        —N(—C(O)—NH—O—Z271)(—C(O)—NZ272-O—Z273), —C(S)—Z274,        —C(S)—O—Z275, —C(S)—NH—Z276, —C(S)—NZ277Z278, —C(O)—NH—O—Z279,        —C(O)—NZ280-O—Z281, —C(S)—NH—O—Z282, —C(S)—NZ283-O—Z284,        —C(O)—NH—NH—Z285, —C(O)—NH—NZ286Z287, —C(O)—NZ288-NZ289Z290,        —C(S)—NH—NH—Z291, —C(S)—NH—NZ292Z293, —C(S)—NZ294-NZ295Z296,        —C(O)—C(O)—O—Z297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ298,        —C(O)—C(O)—NZ299Z300, —C(S)—C(O)—O—Z301, —C(O)—C(S)—O—Z302,        —C(S)—C(S)—O—Z303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ304,        —C(S)—C(O)—NZ305Z306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ307,        —C(S)—C(S)—NZ308Z309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ310,        —C(O)—C(S)—NZ311Z312”;        -   wherein Z201, Z202, Z203, Z204, Z205, Z206, Z207, Z208,            Z209, Z210, Z211, Z212, Z213, Z214, Z215, Z216, Z217, Z218,            Z219, Z220, Z221, Z222, Z223, Z224, Z225, Z226, Z227, Z228,            Z229, Z230, Z231, Z232, Z233, Z234, Z235, Z236, Z237, Z238,            Z239, Z240, Z241, Z242, Z243, Z244, Z245, Z246, Z247, Z248,            Z249, Z250, Z251, Z252, Z253, Z254, Z255, Z256, Z257, Z258,            Z259, Z260, Z261, Z262, Z263, Z264, Z265, Z266, Z267, Z268,            Z269, Z270, Z271, Z272, Z273, Z274, Z275, Z276, Z277, Z278,            Z279, Z280, Z281, Z282, Z283, Z284, Z285, Z286, Z287, Z288,            Z289, Z290, Z291, Z292, Z293, Z294, Z295, Z296, Z297, Z298,            Z299, Z300, Z301, Z302, Z303, Z304, Z305, Z306, Z307, Z308,            Z309, Z310, Z311, Z312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively Z207, Z208 and/or            Z216, Z217 and/or Z229, Z230 and/or Z236, Z237 and/or Z245,            Z246 and/or Z255, Z256 and/or Z260, Z261 and/or Z277, Z278            and/or Z286, Z287 and/or Z289, Z290 and/or Z292, Z293 and/or            Z295, Z296 and/or Z299, Z300 and/or Z305, Z306 and/or Z308,            Z309 and/or Z311, Z312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHZ401, —NZ402Z403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z404, —C(O)O—Z405, —C(O)NH—Z406, —C(O)NZ407Z408, —O—Z409,        —O(—Z410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—Z411-O)Z412 (f=1, 2, 3,        4, 5), —OC(O)—Z413, —OC(O)—O—Z414, —OC(O)—NHZ415,        —O—C(O)—NZ416Z417, —OP(O)(OZ418)(OZ419), —OSi(Z420)(Z421)(Z422),        —OS(O₂)—Z423, —NHC(O)—NH₂, —NHC(O)—Z424, —NZ425C(O)—Z426,        —NH—C(O)—OZ427, —NH—C(O)—NH—Z428, —NH—C(O)—NZ429Z430,        —NZ431-C(O)—O—Z432, —NZ433-C(O)—NH—Z434, —NZ435-C(O)—NZ436Z437,        —NHS(O₂)—Z438, —NZ439S(O₂)—Z440, —S—Z441, —S(O)—Z442,        —S(O₂)—Z443, —S(O₂)NH—Z444, —S(O₂)NZ445Z446, —S(O₂)O—Z447,        —P(O)(OZ448)(OZ449), —Si(Z450)(Z451)(Z452), —C(NH)—NH₂,        —C(NZ453)-NH₂, —C(NH)—NHZ454, —C(NH)—NZ455Z456,        —C(NZ457)-NHZ458, —C(NZ459)-NZ460Z461, —NH—C(O)—NH—O—Z462,        —NH—C(O)—NZ463-O—Z464, —NZ465-C(O)—NZ466-O—Z467,        —N(—C(O)—NH—O—Z468)₂, —N(—C(O)—NZ469-OZ470)₂,        —N(—C(O)—NH—O—Z471)(—C(O)—NZ472-O—Z473), —C(S)Z474,        —C(S)—O—Z475, —C(S)—NH—Z476, —C(S)—NZ477Z478, —C(O)—NH—O—Z479,        —C(O)—NZ480-O—Z481, —C(S)—NH—O—Z482, —C(S)—NZ483-O—Z484,        —C(O)—NH—NH—Z485, —C(O)—NH—NZ486Z487, —C(O)—NZ488-NZ489Z490,        —C(S)—NH—NH—Z491, —C(S)—NHNZ492Z493, —C(S)—NZ494-NZ495Z496,        —C(O)—C(O)—O—Z497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ498,        —C(O)—C(O)—NZ499Z500, —C(S)—C(O)—O—Z501, —C(O)—C(S)—O—Z502,        —C(S)—C(S)—O—Z503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ504,        —C(S)—C(O)—NZ505Z506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ507,        —C(S)—C(S)—NZ508Z509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ510,        —C(O)—C(S)—NZ511Z512”;        -   wherein Z401, Z402, Z403, Z404, Z405, Z406, Z407, Z408,            Z409, Z410, Z411, Z412, Z413, Z414, Z415, Z416, Z417, Z418,            Z419, Z420, Z421, Z422, Z423, Z424, Z425, Z426, Z427, Z428,            Z429, Z430, Z431, Z432, Z433, Z434, Z435, Z436, Z437, Z438,            Z439, Z440, Z441, Z442, Z443, Z444, Z445, Z446, Z447, Z448,            Z449, Z450, Z451, Z452, Z453, Z454, Z455, Z456, Z457, Z458,            Z459, Z460, Z461, Z462, Z463, Z464, Z465, Z466, Z467, Z468,            Z469, Z470, Z471, Z472, Z473, Z474, Z475, Z476, Z477, Z478,            Z479, Z480, Z481, Z482, Z483, Z484, Z485, Z486, Z487, Z488,            Z489, Z490, Z491, Z492, Z493, Z494, Z495, Z496, Z497, Z498,            Z499, Z500, Z501, Z502, Z503, Z504, Z505, Z506, Z507, Z508,            Z509, the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively Z407, Z408 and/or            Z416, Z417 and/or Z429, Z430 and/or Z436, Z437 and/or Z445,            Z446 and/or Z455, Z456 and/or Z460, Z461 and/or Z477, Z478            and/or Z486, Z487 and/or Z489, Z490 and/or Z492, Z493 and/or            Z495, Z496 and/or Z499, Z500 and/or Z505, Z506 and/or Z508,            Z509 and/or Z511, Z512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHZ601, —NZ602Z603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z604, —C(O)O—Z605, —C(O)NH—Z606, —C(O)NZ607Z608, —O—Z609,        —O(—Z610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—Z611-O)_(f)—Z612 (f=1,        2, 3, 4, 5), —OC(O)—Z613, —OC(O)—O—Z614, —OC(O)—NHZ615,        —O—C(O)—NZ616Z617, —OP(O)(OZ618)(OZ619), —OSi(Z620)(Z621)(Z622),        —OS(O₂)—Z623, —NHC(O)—NH₂, —NHC(O)—Z624, —NZ625C(O)—Z626,        —NH—C(O)—O—Z627, —NH—C(O)—NH—Z628, —NH—C(O)—NZ629Z630,        —NZ631-C(O)—O—Z632, —NZ633-C(O)—NH—Z634, —NZ635-C(O)—NZ636Z637,        —NHS(O₂)—Z638, —NZ639S(O₂)—Z640, —S—Z641, —S(O)—Z642,        —S(O₂)—Z643, —S(O₂)NH—Z644, —S(O₂)NZ645Z646, —S(O₂)O—Z647,        —P(O)(OZ648)(OZ649), —Si(Z650)(Z651)(Z652), —C(NH)—NH₂,        —C(NZ653)-NH₂, —C(NH)—NHZ654, —C(NH)—NZ655Z656,        —C(NZ657)-NHZ658, —C(NZ659)-NZ660Z661, —NH—C(O)—NH—O—Z662,        —NH—C(O)—NZ663-O—Z664, —NZ665-C(O)—NZ666-O—Z667,        —N(—C(O)—NH—O—Z668)₂, —N(—C(O)—NZ669-O—Z670)₂,        —N(—C(O)—NH—O—Z671)(—C(O)—NZ672-O—Z673), —NZ677Z678,        —C(O)—NH—O—Z679, —C(O)—NZ680-O—Z681, —C(S)—NH—O—Z682,        —C(S)—NZ683-O—Z684, —C(O)—NH—NH—Z685, —C(O)—NH—NZ686Z687,        —C(O)—NZ688-NZ689Z690, —C(S)—NH—NH—Z691, —C(S)—NH—NZ692Z693,        —C(S)—NZ694-NZ695Z696, —C(O)—C(O)—O—Z697, —C(O)—C(O)—NH₂,        —C(O)—C(O)—NHZ698, —C(O)—C(O)—NZ699Z700, —C(S)—C(O)—O—Z701,        —C(O)—C(S)—O—Z702, —C(S)—C(S)—O—Z703, —C(S)—C(O)—NH₂,        —C(S)—C(O)—NHZ704, —C(S)—C(O)—NZ705Z706, —C(S)—C(S)—NH₂,        —C(S)—C(S)—NHZ707, —C(S)—C(S)—NZ708Z709, —C(O)—C(S)—NH₂,        —C(O)—C(S)—NHZ710, —C(O)—C(S)—NZ711Z712”;        -   wherein Z601, Z602, Z603, Z604, Z605, Z606, Z607, Z608,            Z609, Z610, Z611, Z612, Z613, Z614, Z615, Z616, Z617, Z618,            Z619, Z620, Z621, Z622, Z623, Z624, Z625, Z626, Z627, Z628,            Z629, Z630, Z631, Z632, Z633, Z634, Z635, Z636, Z637, Z638,            Z639, Z640, Z641, Z642, Z643, Z644, Z645, Z646, Z647, Z648,            Z649, Z650, Z651, Z652, Z653, Z654, Z655, Z656, Z657, Z658,            Z659, Z660, Z661, Z662, Z663, Z664, Z665, Z666, Z667, Z668,            Z669, Z670, Z671, Z672, Z673, Z674, Z675, Z676, Z677, Z678,            Z679, Z680, Z681, Z682, Z683, Z684, Z685, Z686, Z687, Z688,            Z689, Z690, Z691, Z692, Z693, Z694, Z695, Z696, Z697, Z698,            Z699, Z700, Z701, Z702, Z703, Z704, Z705, Z706, Z707, Z708,            Z709, Z710, Z711, Z712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively Z607, Z608 and/or            Z616, Z617 and/or Z629, Z630 and/or Z636, Z637 and/or Z645,            Z646 and/or Z655, Z656 and/or Z660, Z661 and/or Z677, Z678            and/or Z686, Z687 and/or Z689, Z690 and/or Z692, Z693 and/or            Z695, Z696 and/or Z699, Z700 and/or Z705, Z706 and/or Z708,            Z709 and/or Z711, Z712 and/or respectively together can also            form “heterocyclyl”;            with the proviso that radical R16 is not “indol-yl”;

(d) “—S(O₂)—R18”;

-   -   wherein radical R18 is independently selected from the group        consisting of:    -   (III)“—F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NHW1, —NW2W3,        —NO₂, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO, —COOH,        —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —C(O)—W4, —C(O)O—W5, —C(O)NH—W6,        —C(O)NW7W8, —O—W9, —O(—W10-O)_(a)—H (a=1, 2, 3, 4, 5),        —O(—W11-O)_(b)—W12 (b=1, 2, 3, 4, 5), —OC(O)—W13, —OC(O)—O—W14,        —OC(O)—NHW15, —O—C(O)—NW16W17, —OP(O)(OW18)(OW19),        —OSi(W20)(W21)(W22), —OS(O₂)—W23, —NHC(O)—NH₂, —NHC(O)—W24,        —NW25C(O)—W26, —NH—C(O)—O—W27, —NH—C(O)—NH—W28,        —NH—C(O)—NW29W30, —NW31-C(O)—O—W32, —NW33-C(O)—NH—W34,        —NW35-C(O)—NW36W37, —NHS(O₂)—W38, —NW39S(O₂)—W40, —S—W41,        —S(O)—W42, —S(O₂)—W43, —S(O₂)NH—W44, —S(O₂)NW45W46, —S(O₂)O—W47,        —P(O)(OW48)(OW49), —Si(W50)(W51)(W52), —C(NH)—NH₂, —C(NW53)-NH₂,        —C(NH)—NHW54, —C(NH)—NW55W56, —C(NW57)-NHW58, —C(NW59)-NW60W61,        —NH—C(O)—NH—O—W62, —NH—C(O)—NW63-O—W64, —NW65-C(O)—NW66-O—W67,        —N(—C(O)—NH—O—W68)₂, —N(—C(O)—NW69-O—W70)₂,        —N(—C(O)—NH—O—W71)(—C(O)—NW72-O—W73), —C(S)—W74, —C(S)—O—W75,        —C(S)—NH—W76, —C(S)—NW77W78, —C(O)—NH—O—W79, —C(O)—NW80-O—W81,        —C(S)—NH—O—W82, —C(S)—NW83-O—W84, —C(O)—NH—NH—W85,        —C(O)—NH—NW86W87, —C(O)—NW88-NW89W90, —C(S)—NH—NH—W91,        —C(S)—NH—NW92W93, —C(S)—NW94-NW95W96, —C(O)—C(O)—O—W97,        —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW98, —C(O)—C(O)—NW99W100,        —C(S)—C(O)—O—W101, —C(O)—C(S)—O—W102, —C(S)—C(S)—O—W103,        —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW104, —C(S)—C(O)—NW105W106,        —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW107, —C(S)—C(S)—NW108W109,        —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW110, —C(O)—C(S)—NW111W112”;        -   wherein W1, W2, W3, W4, W5, W6, W7, W8, W9, W10, W11, W12,            W13, W14, W15, W16, W17, W18, W19, W20, W21, W22, W23, W24,            W25, W26, W27, W28, W29, W30, W31, W32, W33, W34, W35, W36,            W37, W38, W39, W40, W41, W42, W43, W44, W45, W46, W47, W48,            W49, W50, W51, W52, W53, W54, W55, W56, W57, W58, W59, W60,            W61, W62, W63, W64, W65, W66, W67, W68, W69, W70, W71, W72,            W73, W74, W75, W76, W77, W78, W79, W80, W81, W82, W83, W84,            W85, W86, W87, W88, W89, W90, W91, W92, W93, W94, W95, W96,            W97, W98, W99, W100, W101, W102, W103, W104, W105, W106,            W107, W108, W109, W110, W111, W112 are independently from            each other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and wherein alternatively W7,            W8 and/or W16, W17 and/or W29, W30 and/or W36, W37 and/or            W45, W46 and/or W55, W56 and/or W60, W61 and/or W77, W78            and/or W86, W87 and/or W89, W90 and/or W92, W93 and/or W95,            W96 and/or W99, W100 and/or W105, W106 and/or W108, W109            and/or W111, W112 and/or respectively together can also form            “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (III) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHW201, —NW202W203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—W204, —C(O)O—W205, —C(O)NH—W206, —C(O)NW207W208, —O—W209,        —O(—W210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(—W211-O)_(d)—W212 (d=1,        2, 3, 4, 5), —OC(O)—W213, —OC(O)—O—W214, —OC(O)—NHW215,        —O—C(O)—NW216W217, —OP(O)(OW218)(OW219), —OSi(W220)(W221)(W222),        —OS(O₂)—W223, —NHC(O)—NH₂, —NHC(O)—W224, —NW225C(O)—W226,        —NH—C(O)—O—W227, —NH—C(O)—NH—W228, —NH—C(O)—NW229W230,        —NW231-C(O)—O—W232, —NW233-C(O)—NH—W234, —NW235-C(O)—NW236W237,        —NHS(O₂)—W238, —NW239S(O₂)—W240, —S—W241, —S(O)—W242,        —S(O₂)—W243, —S(O₂)NH—W244, —S(O₂)NW245W246, —S(O₂)O—W247,        —P(O)(OW248)(OW249), —Si(W250)(W251)(W252), —C(NH)—NH₂,        —C(NW253)-NH₂, —C(NH)—NHW254, —C(NH)—NW255W256,        —C(NW257)-NHW258, —C(NW259)-NW260W261, —NH—C(O)—NH—O—W262,        —NH—C(O)—NW263-O—W264, —NW265-C(O)—NW266-O—W267,        —N(—C(O)—NH—O—W268)₂, —N(—C(O)—NW269-O—W270)₂,        —N(—C(O)—NH—O—W271)(—C(O)—NW272-O—W273), —C(S)—W274,        —C(S)—O—W275, —C(S)—NH—W276, —C(S)—NW277W278, —C(O)—NH—O—W279,        —C(O)—NW280-O—W281, —C(S)—NH—O—W282, —C(S)—NW283-O—W284,        —C(O)—NH—NH—W285, —C(O)—NH—NW286W287, —C(O)—NW288-NW289W290,        —C(S)—NH—NH—W291, —C(S)—NH—NW292W293, —C(S)—NW294-NW295W296,        —C(O)—C(O)—O—W297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW298,        —C(O)—C(O)—NW299W300, —C(S)—C(O)—O—W301, —C(O)—C(S)—O—W302,        —C(S)—C(S)—O—W303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW304,        —C(S)—C(O)—NW305W306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW307,        —C(S)—C(S)—NW308W309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW310,        —C(O)—C(S)—NW311W312”;        -   wherein W201, W202, W203, W204, W205, W206, W207, W208,            W209, W210, W211, W212, W213, W214, W215, W216, W217, W218,            W219, W220, W221, W222, W223, W224, W225, W226, W227, W228,            W229, W230, W231, W232, W233, W234, W235, W236, W237, W238,            W239, W240, W241, W242, W243, W244, W245, W246, W247, W248,            W249, W250, W251, W252, W253, W254, W255, W256, W257, W258,            W259, W260, W261, W262, W263, W264, W265, W266, W267, W268,            W269, W270, W271, W272, W273, W274, W275, W276, W277, W278,            W279, W280, W281, W282, W283, W284, W285, W286, W287, W288,            W289, W290, W291, W292, W293, W294, W295, W296, W297, W298,            W299, W300, W301, W302, W303, W304, W305, W306, W307, W308,            W309, W310, W311, W312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively W207, W208 and/or            W216, W217 and/or W229, W230 and/or W236, W237 and/or W245,            W246 and/or W255, W256 and/or W260, W261 and/or W277, W278            and/or W286, W287 and/or W289, W290 and/or W292, W293 and/or            W295, W296 and/or W299, W300 and/or W305, W306 and/or W308,            W309 and/or W311, W312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHW401, —NW402W403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—W404, —C(O)O—W405, —C(O)NH—W406, —C(O)NW407W408, —O—W409,        —O(—W410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—W411-O)_(f)—W412 (f=1,        2, 3, 4, 5), —OC(O)—W413, —OC(O)—O—W414, —OC(O)—NHW415,        —O—C(O)—NW416W417, —OP(O)(OW418)(OW419), —OSi(W420)(W421)(W422),        —OS(O₂)—W423, —NHC(O)—NH₂, —NHC(O)—W424, —NW425C(O)—W426,        —NH—C(O)—O—W427, —NH—C(O)—NH—W428, —NH—C(O)—NW429W430,        —NW431-C(O)—O—W432, —NW433-C(O)—NH—W434, —NW435-C(O)—NW436W437,        —NHS(O₂)—W438, —NW439S(O₂)—W440, —S—W441, —S(O)—W442,        —S(O₂)—W443, —S(O₂)NH—W444, —S(O₂)NW445W446, —S(O₂)O—W447,        —P(O)(OW448)(OW449), —Si(W450)(W451)(W452), —C(NH)—NH₂,        —C(NW453)-NH₂, —C(NH)—NHW454, —C(NH)—NW455W456,        —C(NW457)-NHW458, —C(NW459)-NW460W461, —NH—C(O)—NH—O—W462,        —NH—C(O)—NW463-O—W464, —NW465-C(O)—NW466-O—W467,        —N(—C(O)—NH—O—W468)₂, —N(—C(O)—NW469-O—W470)₂,        —N(—C(O)—NH—O—W471)(—C(O)—NW472-O—W473), —C(S)—W474,        —C(S)—O—W475, —C(S)—NH—W476, —C(S)—NW477W478, —C(O)—NH—O—W479,        —C(O)—NW480-O—W481, —C(S)—NH—O—W482, —C(S)—NW483-O—W484,        —C(O)—NH—NH—W485, —C(O)—NH—NW486W487, —C(O)—NW488-NW489W490,        —C(S)—NH—NH—W491, —C(S)—NH—NW492W493, —C(S)—NW494-NW495W496,        —C(O)—C(O)—O—W497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW498,        —C(O)—C(O)—NW499W500, —C(S)—C(O)—O—W501, —C(O)—C(S)—O—W502,        —C(S)—C(S)—O—W503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW504,        —C(S)—C(O)—NW505W506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW507,        —C(S)—C(S)—NW508W509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW510,        —C(O)—C(S)—NW511W512”;        -   wherein W401, W402, W403, W404, W405, W406, W407, W408,            W409, W410, W411, W412, W413, W414, W415, W416, W417, W418,            W419, W420, W421, W422, W423, W424, W425, W426, W427, W428,            W429, W430, W431, W432, W433, W434, W435, W436, W437, W438,            W439, W440, W441, W442, W443, W444, W454, W455, W456, W457,            W458, W459, W460, W461, W462, W463, W464, W465, W466, W467,            W468, W469, W470, W471, W472, W473, W474, W475, W476, W477,            W478, W479, W480, W481, W482, W483, W484, W485, W486, W487,            W488, W489, W490, W491, W492, W493, W494, W495, W496, W497,            W498, W499, W500, W501, W502, W503, W504, W505, W506, W507,            W508, W509, W510, W511, W512 are independently from each            other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and wherein alternatively W407,            W408 and/or W416, W417 and/or W429, W430 and/or W436, W437            and/or W445, W446 and/or W455, W456 and/or W460, W461 and/or            W477, W478 and/or W486, W487 and/or W489, W490 and/or W492,            W493 and/or W495, W496 and/or W499, W500 and/or W505, W506            and/or W508, W509 and/or W511, W512 and/or respectively            together can also form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHW601, —NW602W603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—W604, —C(O)O—W605, —C(O)NH—W606, —C(O)NW607W608, —O—W609,        —O(—W610-O), —H (e=1, 2, 3, 4, 5), —O(—W611-O)_(f)—W612 (f=1, 2,        3, 4, 5), —OC(O)—W613, —OC(O)—O—W614, —OC(O)—NHW615,        —O—C(O)—NW616W617, —OP(O)(OW618)(OW619), —OSi(W620)(W621)(W622),        —OS(O₂)—W623, —NHC(O)—NH₂, —NHC(O)—W624, —NW625C(O)—W626,        —NH—C(O)—O—W627, —NH—C(O)—NH—W628, —NH—C(O)—NW629W630,        —NW631-C(O)—O—W632, —NW633-C(O)—NH—W634, —NW635-C(O)—NW636W637,        —NHS(O₂)—W638, —S(O₂)NH—W644, —S(O₂)NW645W646, —S(O₂)O—W647,        —P(O)(OW648)(OW649), —Si(W650)(W651)(W652), —C(NH)—NH₂,        —C(NW653)-NH₂, —C(NH)—NHW654, —C(NH)—NW655W656,        —C(NW657)-NHW658, —C(NW659)-NW660W661, —NH—C(O)—NH—O—W662,        —NH—C(O)—NW663-O—W664, —NW665-C(O)—NW666-O—W667,        —N(—C(O)—NH—O—W668)₂, —N(—C(O)—NW669-O—W670)₂,        —N(—C(O)—NH—O—W671)(—C(O)—NW672-O—W673), —C(S)—W674,        —C(S)—O—W675, —C(S)—NH—W676, —C(S)—NW677W678, —C(O)—NH—O—W679,        —C(O)—NW680-O—W681, —C(S)—NH—O—W682, —C(S)—NW683-O—W684,        —C(O)—NH—NH—W685, —C(O)—NH—NW686W687, —C(O)—NW688-NW689W690,        —C(S)—NH—NH—W691, —C(S)—NH—NW692W693, —C(S)—NW694-NW695W696,        —C(O)—C(O)—O—W697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW698,        —C(O)—C(O)—NW699W700, —C(S)—C(O)—O—W701, —C(O)—C(S)—O—W702,        —C(S)—C(S)—O—W703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW704,        —C(S)—C(O)—NW705W706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW707,        —C(S)—C(S)—NW708W709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW710,        —C(O)—C(S)—NW711W712”;        -   wherein W601, W602, W603, W604, W605, W606, W607, W608,            W609, W610, W611, W612, W613, W614, W615, W616, W617, W618,            W619, W620, W621, W622, W623, W624, W625, W626, W627, W628,            W629, W630, W631, W632, W633, W634, W635, W636, W637, W638,            W639, W640, W641, W642, W643, W644, W645, W646, W647, W648,            W649, W650, W651, W652, W653, W654, W655, W656, W657, W658,            W659, W660, W661, W662, W663, W664, W665, W666, W667, W668,            W669, W670, W671, W672, W673, W674, W675, W676, W677, W678,            W679, W680, W681, W682, W683, W684, W685, W686, W687, W688,            W689, W690, W691, W692, W693, W694, W695, W696, W697, W698,            W699, W700, W701, W702, W703, W704, W705, W706, W707, W708,            W709, W710, W711, W712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,        -   wherein alternatively W607, W608 and/or W616, W617 and/or            W629, W630 and/or W636, W637 and/or W645, W646 and/or W655,            W656 and/or W660, W661 and/or W677, W678 and/or W686, W687            and/or W689, W690 and/or W692, W693 and/or W695, W696 and/or            W699, W700 and/or W705, W706 and/or W708, W709 and/or W711,            W712 and/or respectively together can also form            “heterocyclyl”;    -   with the first proviso that radical R18 is not selected from the        group consisting of: “—O-alkyl, —O—(C₉-C₃₀)alkyl, —O-aryl,        —O-arylalkyl, —O-heteroaryl, —O-heteroarylalkyl, —O-cycloalkyl,        —O-cycloalkylalkyl, —O-heterocyclyl, —O-heterocyclylalkyl”;    -   with the second proviso that, if radical R₁₈ independently is        selected from the group consisting of: “—NR_(a)R_(b)”, with Ra,        Rb independently from each other being selected from the group        consisting of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, aryl, arylalkyl,        heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl”, radical R1 is not selected        from the group consisting of: “heterocyclylalkyl being        substituted with ═O, where heterocyclyl is 5-membered; alkyl        being substituted with heterocyclyl, where heterocyclyl is        5-membered and substituted with ═O”;        and one of radicals R3, R4 or neither of radicals R3, R4        independently is selected from the group consisting of:

-   (2) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,    heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,    heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NHA1,    —NA2A3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO,    —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —C(O)-A4, —C(O)O-A5, —C(O)NH-A6,    —C(O)NA7A8, —O-A9, —O(-A10-O)_(a)—H (a=1, 2, 3, 4, 5),    —O(-A11-O)_(b)-A12 (b=1, 2, 3, 4, 5), —OC(O)-A13, —OC(O)—O-A14,    —OC(O)—NHA15, —O—C(O)—NA16A17, —OP(O)(OA18)(OA19),    —OSi(A20)(A21)(A22), —OS(O₂)-A23, —NHC(O)—NH₂, —NHC(O)-A24,    —NA25C(O)-A26, —NH—C(O)—O-A27, —NH—C(O)—NH-A28, —NH—C(O)—NA29A30,    —NA31-C(O)—O-A32, —NA33-C(O)—NH-A34, —NA35-C(O)—NA36A37,    —NHS(O₂)-A38, —NA39S(O₂)-A40, —S-A41, —S(O)-A42, —S(O₂)— A43,    —S(O₂)NH-A44, —S(O₂)NA45A46, —S(O₂)O-A47, —P(O)(OA48)(OA49),    —Si(A50)(A51)(A52), —C(NH)—NH₂, —C(NA53)-NH₂, —C(NH)—NHA54,    —C(NH)—NA55A56, —C(NA57)-NHA58, —C(NA59)-NA60A61, —NH—C(O)—NH—O-A62,    —NH—C(O)—NA63-O-A64, —NA65-C(O)—NA66-O-A67, —N(—C(O)—NH—O-A68)₂,    —N(—C(O)—NA69-O-A70)₂, —N(—C(O)—NH—O-A71)(—C(O)—NA72-O-A73),    —C(S)-A74, —C(S)—O-A75, —C(S)—NH-A76, —C(S)—NA77A78, —C(O)—NH—O-A79,    —C(O)—NA80-O-A81, —C(S)—NH—O-A82, —C(S)—NA83-O-A84, —C(O)—NH—NH-A85,    —C(O)—NH—NA86A87, —C(O)—NA88-NA89A90, —C(S)—NH—NH-A91,    —C(S)—NH—NA92A93, —C(S)—NA94-NA95A96, —C(O)—C(O)—O-A97,    —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA98, —C(O)—C(O)—NA99A100,    —C(S)—C(O)—O-A101, —C(O)—C(S)—O-A102, —C(S)—C(S)—O-A103,    —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA104, —C(S)—C(O)—NA105A106,    —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA107, —C(S)—C(S)—NA108A109,    —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA110, —C(O)—C(S)—NA111A112”;    -   wherein A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13,        A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26,        A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39,        A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52,        A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65,        A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78,        A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91,        A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103,        A104, A105, A106, A107, A108, A109, A110, A111, A112 are        independently from each other selected from the group consisting        of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl” and wherein        alternatively A7, A8 and/or A16, A17 and/or A29, A30 and/or A36,        A37 and/or A45, A46 and/or A55, A56 and/or A60, A61 and/or A77,        A78 and/or A86, A87 and/or A89, A90 and/or A92, A93 and/or A95,        A96 and/or A99, A100 and/or A105, A106 and/or A108, A109 and/or        A111, A112 and/or respectively together can also form        “heterocyclyl”;    -   wherein optionally above substituents of substituents group        (2)—if not hydrogenn—can in turn independently from each other        be substituted with at least one substituent, identical or        different, selected from the group consisting of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHA201, —NA202A203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)-A204, —C(O)O-A205, —C(O)NH-A206, —C(O)NA207A208, —O-A209,        —O(-A210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(-A211-O)_(d)-A212 (d=1,        2, 3, 4, 5), —OC(O)-A213, —OC(O)—O-A214, —OC(O)—NHA215,        —O—C(O)—NA216A217, —OP(O)(OA218)(OA219), —OSi(A220)(A221)(A222),        —OS(O₂)-A223, —NHC(O)—NH₂, —NHC(O)-A224, —NA225C(O)-A226,        —NH—C(O)—O-A227, —NH—C(O)—NH-A228, —NH—C(O)—NA229A230,        —NA231-C(O)—O-A232, —NA233-C(O)—NH-A234, —NA235-C(O)—NA236A237,        —NHS(O₂)-A238, —NA239S(O₂)-A240, —S-A241, —S(O)-A242,        —S(O₂)-A243, —S(O₂)NH-A244, —S(O₂)NA245A246, —S(O₂)O -A247,        —P(O)(OA248)(OA249), —Si(A250)(A251)(A252), —C(NH)—NH₂,        —C(NA253)-NH₂, —C(NH)—NHA254, —C(NH)—NA255A256,        —C(NA257)-NHA258, —C(NA259)-NA260A261, —NH—C(O)—NH—O-A262,        —NH—C(O)—NA263-O-A264, —NA265-C(O)—NA266-O-A267,        —N(—C(O)—NH—O-A268)₂, —N(—C(O)—NA269-O-A270)₂,        —N(—C(O)—NH—O-A271)(—C(O)—NA272-O-A273), —C(S)-A274,        —C(S)—O-A275, —C(S)—NH-A276, —C(S)—NA277A278, —C(O)—NH—O-A279,        —C(O)—NA280-O-A281, —C(S)—NH—O-A282, —C(S)—NA283-O-A284,        —C(O)—NH—NH-A285, —C(O)—NH—NA286A287, —C(O)—NA288-NA289A290,        —C(S)—NH—NH-A291, —C(S)—NH—NA292A293, —C(S)—NA294-NA295A296,        —C(O)—C(O)—O-A297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA298,        —C(O)—C(O)—NA299A300, —C(S)—C(O)—O-A301, —C(O)—C(S)—O-A302,        —C(S)—C(S)—O-A303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA304,        —C(S)—C(O)—NA305A306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA307,        —C(S)—C(S)—NA308A309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA310,        —C(O)—C(S)—NA311A312”;    -   wherein A201, A202, A203, A204, A205, A206, A207, A208, A209,        A210, A211, A212, A213, A214, A215, A216, A217, A218, A219,        A220, A221, A222, A223, A224, A225, A226, A227, A228, A229,        A230, A231, A232, A233, A234, A235, A236, A237, A238, A239,        A240, A241, A242, A243, A244, A245, A246, A247, A248, A249,        A250, A251, A252, A253, A254, A255, A256, A257, A258, A259,        A260, A261, A262, A263, A264, A265, A266, A267, A268, A269,        A270, A271, A272, A273, A274, A275, A276, A277, A278, A279,        A280, A281, A282, A283, A284, A285, A286, A287, A288, A289,        A290, A291, A292, A293, A294, A295, A296, A297, A298, A299,        A300, A301, A302, A303, A304, A305, A306, A307, A308, A309,        A310, A311, A312 are independently from each other selected from        the group consisting of: “hydrogen, alkyl, (C₉-C₃₀)alkyl,        cycloalkyl, cycloalkylalkyl, heterocyclyl, heterocyclylalkyl,        aryl, arylalkyl, heteroaryl, heteroarylalkyl” and wherein        alternatively A207, A208 and/or A216, A217 and/or A229, A230        and/or A236, A237 and/or A245, A246 and/or A255, A256 and/or        A260, A261 and/or A277, A278 and/or A286, A287 and/or A289, A290        and/or A292, A293 and/or A295, A296 and/or A299, A300 and/or        A305, A306 and/or A308, A309 and/or A311, A312 and/or        respectively together can also form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHA401, —NA402A403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)-A404, —C(O)O-A405, —C(O)NH-A406, —C(O)NA407A408, —O-A409,        —O(-A410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(-A411-O)_(f)-A412 (f=1,        2, 3, 4, 5), —OC(O)-A413, —OC(O)—O-A414, —OC(O)—NHA415,        —O—C(O)—NA416A417, —OP(O)(OA418)(OA419), —OSi(A420)(A421)(A422),        —OS(O₂)-A423, —NHC(O)—NH₂, —NHC(O)-A424, —NA425C(O)-A426,        —NH—C(O)—O-A427, —NH—C(O)—NH-A428, —NH—C(O)—NA429A430,        —NA431-C(O)—O-A432, —NA433-C(O)—NH-A434, —NA435-C(O)—NA436A437,        —NHS(O₂)-A438, —NA439S(O₂)-A440, —S-A441, —S(O)-A442, —S(O₂)—        A443, —S(O₂)NH-A444, —S(O₂)NA445A446, —S(O₂)O-A447,        —P(O)(OA448)(OA449), —Si(A450)(A451)(A452), —C(NH)—NH₂,        —C(NA453)-NH₂, —C(NH)—NHA454, —C(NH)—NA455A456,        —C(NA457)-NHA458, —C(NA459)-NA460A461, —NH—C(O)—NH—O-A462,        —NH—C(O)—NA463-O-A464, —NA465-C(O)—NA466-O-A467,        —N(—C(O)—NH—O-A468)₂, —N(—C(O)—NA469-O-A470)₂,        —N(—C(O)—NH—O-A471)(—C(O)—NA472-O-A473), —C(S)-A474,        —C(S)—O-A475, —C(S)—NH-A476, —C(S)—NA477A478, —C(O)—NH—O-A479,        —C(O)—NA480-O-A481, —C(S)—NH—O-A482, —C(S)—NA483-O-A484,        —C(O)—NH—NH-A485, —C(O)—NH—NA486A487, —C(O)—NA488-NA489A490,        —C(S)—NH—NH-A491, —C(S)—NH—NA492A493, —C(S)—NA494-NA495A496,        —C(O)—C(O)—O-A497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA498,        —C(O)—C(O)—NA499A500, —C(S)—C(O)—O-A501, —C(O)—C(S)—O-A502,        —C(S)—C(S)—O-A503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA504,        —C(S)—C(O)—NA505A506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA507,        —C(S)—C(S)—NA508A509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA510,        —C(O)—C(S)—NA511A512”;        -   wherein A401, A402, A403, A404, A405, A406, A407, A408,            A409, A410, A411, A412, A413, A414, A415, A416, A417, A418,            A419, A420, A421, A422, A423, A424, A425, A426, A427, A428,            A429, A430, A431, A432, A433, A434, A435, A436, A437, A438,            A439, A440, A441, A442, A443, A444, A445, A446, A447, A448,            A449, A450, A451, A452, A453, A454, A455, A456, A457, A458,            A459, A460, A461, A462, A463, A464, A465, A466, A467, A468,            A469, A470, A471, A472, A473, A474, A475, A476, A477, A478,            A479, A480, A481, A482, A483, A484, A485, A486, A487, A488,            A489, A490, A491, A492, A493, A494, A495, A496, A497, A498,            A499, A500, A501, A502, A503, A504, A505, A506, A507, A508,            A509, A510, A511, A512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively A407, A408 and/or            A416, A417 and/or A429, A430 and/or A436, A437 and/or A445,            A446 and/or A455, A456 and/or A460, A461 and/or A477, A478            and/or A486, A487 and/or A489, A490 and/or A492, A493 and/or            A495, A496 and/or A499, A500 and/or A505, A506 and/or A508,            A509 and/or A511, A512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHA601, —NA602A603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)-A604, —C(O)O—A605, —C(O)NH-A606, —C(O)NA607A608, —O-A609,        —O(-A610-O), —H (e=1, 2, 3, 4, 5), —O(-A611-O)A612 (f=1, 2, 3,        4, 5), —OC(O)-A613, —OC(O)—O-A614, —OC(O)—NHA615,        —O—C(O)—NA616A617, —OP(O)(OA618)(OA619), —OSi        (A620)(A621)(A622), —OS(O₂)-A623, —NHC(O)—NH₂, —NHC(O)-A624,        —NA625C(O)-A626, —NH—C(O)—O-A627, —NH—C(O)—NH-A628,        —NH—C(O)—NA629A630, —NA631-C(O)—O-A632, —NA633-C(O)—NH-A634,        —NA635-C(O)—NA636A637, —NHS(O₂)-A638, —NA639S(O₂)-A640, —S-A641,        —S(O)-A642, —S(O₂)-A643, —S(O₂)NH-A644, —S(O₂)NA645A646,        —S(O₂)O-A647, —P(O)(OA648)(OA649), —Si(A650)(A651)(A652),        —C(NH)—NH₂, —C(NA653)-NH₂, —C(NH)—NHA654, —C(NH)—NA655A656,        —C(NA657)-NHA658, —C(NA659)-NA660A661, —NH—C(O)—NH—O-A662,        —NH—C(O)—NA663-O-A664, —NA665-C(O)—NA666-O-A667,        —N(—C(O)—NH—O-A668)₂, —N(—C(O)—NA669-O-A670)₂,        —N(—C(O)—NH—O-A671)(—C(O)—NA672-O-A673), —C(S)-A674,        —C(S)—O-A675, —C(S)—NH-A676, —C(S)—NA677A678, —C(O)—NH—O-A679,        —C(O)—NA680-O-A681, —C(S)—NH—O-A682, —C(S)—NA683-O-A684,        —C(O)—NH—NH-A685, —C(O)—NH—NA686A687, —C(O)—NA688-NA689A690,        —C(S)—NH—NH-A691, —C(S)—NH—NA692A693, —C(S)—NA694-NA695A696,        —C(O)—C(O)—O-A697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA698,        —C(O)—C(O)—NA699A700, —C(S)—C(O)—O-A701, —C(O)—C(S)—O-A702,        —C(S)—C(S)—O-A703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA704,        —C(S)—C(O)—NA705A706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA707,        —C(S)—C(S)—NA708A709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA710,        —C(O)—C(S)—NA711A712”;        -   wherein A601, A602, A603, A604, A605, A606, A607, A608,            A609, A610, A611, A612, A613, A614, A615, A616, A617, A618,            A619, A620, A621, A622, A623, A624, A625, A626, A627, A628,            A629, A630, A631, A632, A633, A634, A635, A636, A637, A638,            A639, A640, A641, A642, A643, A644, A645, A646, A647, A648,            A649, A650, A651, A652, A653, A654, A655, A656, A657, A658,            A659, A660, A661, A662, A663, A664, A665, A666, A667, A668,            A669, A670, A671, A672, A673, A674, A675, A676, A677, A678,            A679, A690, A691, A692, A693, A694, A695, A696, A697, A698,            A699, A700, A701, A702, A703, A704, A705, A706, A707, A708,            A709, A710, A711, A712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively A607, A608 and/or            A616, A617 and/or A629, A630 and/or A636, A637 and/or A645,            A646 and/or A655, A656 and/or A660, A661 and/or A677, A678            and/or A686, A687 and/or A689, A690 and/or A692, A693 and/or            A695, A696 and/or A699, A700 and/or A705, A706 and/or A708,            A709 and/or A711, A712 and/or respectively together can also            form “heterocyclyl”;            and radicals R1, R2, R5 independently from each other are            selected from the group consisting of:

-   (3) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,    heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,    heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NHB1,    —NB2B3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO,    —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —C(O)—B4, —C(O)O—B5, —C(O)NH—B6,    —C(O)NB7B8, —O—B9, —O(—B10-O)_(a)—H (a=1, 2, 3, 4, 5),    —O(—B11-O)_(b)—B12 (b=1, 2, 3, 4, 5), —OC(O)—B13, —OC(O)—O—B14,    —OC(O)—NHB15, —O—C(O)—NB16B17, —OP(O)(OB18)(OB19),    —OSi(B20)(B21)(B22), —OS(O₂)—B23, —NHC(O)—NH₂, —NHC(O)—B24,    —NB25C(O)—B26, —NH—C(O)—O—B27, —NH—C(O)—NH—B28, —NH—C(O)—NB29B30,    —NB31-C(O)—O—B32, —NB33-C(O)—NH—B34, —NB35-C(O)—NB36B37,    —NHS(O₂)—B38, —NB39S(O₂)—B40, —S—B41, —S(O)—B42, —S(O₂)— B43,    —S(O₂)NH—B44, —S(O₂)NB45B46, —S(O₂)O—B47, —P(O)(OB48)(OB49),    —Si(B50)(B51)(B52), —C(NH)—NH₂, —C(NB53)-NH₂, —C(NH)—NHB54,    —C(NH)—NB55B56, —C(NB57)-NHB58, —C(NB59)-NB60B61, —NH—C(O)—NH—O—B62,    —NH—C(O)—NB63-O—B64, —NB65-C(O)—NB66-O—B67, —N(—C(O)—NH—O—B68)₂,    —N(—C(O)—NB69-O—B70)₂, —N(—C(O)—NH—O—B71)(—C(O)—NB72-O—B73),    —C(S)—B74, —C(S)—O—B75, —C(S)—NH—B76, —C(S)—NB77B78, —C(O)—NH—O—B79,    —C(O)—NB80-O—B81, —C(S)—NH—O—B82, —C(S)—NB83-O—B84, —C(O)—NH—NH—B85,    —C(O)—NH—NB86B87, —C(O)—NB88-NB89B90, —C(S)—NH—NH—B91,    —C(S)—NH—NB92B93, —C(S)—NB94-NB95B96, —C(O)—C(O)—O—B97,    —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB98, —C(O)—C(O)—NB99B100,    —C(S)—C(O)—O—B101, —C(O)—C(S)—O—B102, —C(S)—C(S)—O—B103,    —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB104, —C(S)—C(O)—NB105B106,    —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB107, —C(S)—C(S)—NB108B109,    —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB110, —C(O)—C(S)—NB111B112”;    -   wherein B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, B13,        B14, B15, B16, B17, B18, B19, B20, B21, B22, B23, B24, B25, B26,        B27, B28, B29, B30, B31, B32, B33, B34, B35, B36, B37, B38, B39,        B40, B41, B42, B43, B44, B45, B46, B47, B48, B49, B50, B51, B52,        B53, B54, B55, B56, B57, B58, B59, B60, B61, B62, B63, B64, B65,        B66, B67, B68, B69, B70, B71, B72, B73, B74, B75, B76, B77, B78,        B79, B80, B81, B82, B83, B84, B85, B86, B87, B88, B89, B90, B91,        B92, B93, B94, B95, B96, B97, B98, B99, B100, B101, B102, B103,        B104, B105, B106, B107, B108, B109, B110, B111, B112 are        independently from each other selected from the group consisting        of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl” and wherein        alternatively B2, B3 and/or B7, B8 and/or B16, B17 and/or B29,        B30 and/or B36, B37 and/or B45, B46 and/or B55, B56 and/or B60,        B61 and/or B77, B78 and/or B86, B87 and/or B89, B90 and/or B92,        B93 and/or B95, B96 and/or B99, B100 and/or B105, B106 and/or        8108, B109 and/or B111, B112 and/or respectively together can        also form “heterocyclyl”;    -   wherein optionally above substituents of substituents group        (3)—if not hydrogen—can in turn independently from each other be        substituted with at least one substituent, identical or        different, selected from the group consisting of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHB201, —NB202B203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—B204, —C(O)O—B205, —C(O)NH—B206, —C(O)NB207B208, —O—B209,        —O(—B210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(—B211-O)_(d)—B212 (d=1,        2, 3, 4, 5), —OC(O)—B213, —OC(O)—O—B214, —OC(O)—NHB215,        —O—C(O)—N B216B217, —OP(O)(OB218)(OB219),        —OSi(B220)(B221)(B222), —OS(O₂)— B223, —NHC(O)—NH₂,        —NHC(O)—B224, —NB225C(O)—B226, —NH—C(O)—O—B227,        —NH—C(O)—NH—B228, —NH—C(O)—NB229B230, —NB231-C(O)—O—B232,        —NB233-C(O)—NH—B234, —NB235-C(O)—NB236B237, —NHS(O₂)— B238,        —NB239S(O₂)—B240, —S—B241, —S(O)—B242, —S(O₂)—B243,        —S(O₂)NH—B244, —S(O₂)NB245B246, —S(O₂)O—B247,        —P(O)(OB248)(OB249), —Si(B250)(B251)(B252), —C(NH)—NH₂,        —C(NB253)-NH₂, —C(NH)—NHB254, —C(NH)—NB255B256,        —C(NB257)-NHB258, —C(NB259)-NB260B261, —NH—C(O)—NH—O—B262,        —NH—C(O)—NB263-O—B264, —NB265-C(O)—NB266-O—B267,        —N(—C(O)—NH—O—B268)₂, —N(—C(O)—NB269-O—B270)₂,        —N(—C(O)—NH—O—B271)(—C(O)—NB272-O—B273), —C(S)—B274,        —C(S)—O—B275, —C(S)—NH—B276, —C(S)—NB277B278, —C(O)—NH—O—B279,        —C(O)—NB280-O—B281, —C(S)—NH—O—B282, —C(S)—NB283-O—B284,        —C(O)—NH—NH—B285, —C(O)—NH—NB286B287, —C(O)—NB288-NB289B290,        —C(S)—NH—NH—B291, —C(S)—NH—NB292B293, —C(S)—NB294-NB295B296,        —C(O)—C(O)—O—B297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB298,        —C(O)—C(O)—NB299B300, —C(S)—C(O)—O—B301, —C(O)—C(S)—O—B302,        —C(S)—C(S)—O—B303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB304,        —C(S)—C(O)—NB305B306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB307,        —C(S)—C(S)—NB308B309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB310,        —C(O)—C(S)—NB311B312”;        -   wherein B201, B202, B203, B204, B205, B206, B207, B208,            B209, B210, B211, B212, B213, B214, B215, B216, B217, B218,            B219, B220, B221, B222, B223, B224, B225, B226, B227, B228,            B229, B230, B231, B232, B233, B234, B235, B236, B237, B238,            B239, B240, B241, B242, B243, B244, B245, B246, B247, B248,            B249, B250, B251, B252, B253, B254, B255, B256, B257, B258,            B259, B260, B261, B262, B263, B264, B265, 8266, B267, B268,            B269, B270, B271, B272, B273, B274, B275, B276, B277, B278,            B279, B280, B281, B282, B283, B284, B285, B286, B287, B288,            B289, B290, B291, B292, B293, B294, B295, B296, B297, B298,            B299, B300, B301, B302, B303, B304, B305, B306, B307, B308,            B309, B310, B311, B312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively B207, B208 and/or            B216, B217 and/or B229, B230 and/or B236, B237 and/or 8245,            B246 and/or B255, B256 and/or B260, B261 and/or 8277, B278            and/or 8286, B287 and/or B289, B290 and/or B292, B293 and/or            8295, B296 and/or 8299, B300 and/or 8305, B306 and/or B308,            B309 and/or B311, B312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHB401, —NB402B403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—B404, —C(O)O—B405, —C(O)NH—B406, —C(O)NB407B408, —O—B409,        —O(—B410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—B411-O)_(f)—B412 (f=1,        2, 3, 4, 5), —OC(O)—B413, —OC(O)—O—B414, —OC(O)—NHB415,        —O—C(O)—NB416B417, —OP(O)(OB418)(OB419), —OSi(B420)(B421)(B422),        —OS(O₂)—B423, —NHC(O)—NH₂, —NHC(O)—B424, —NB425C(O)—B426,        —NH—C(O)—O—B427, —NH—C(O)—NH—B428, —NH—C(O)—NB429B430,        —NB431-C(O)—O—B432, —NB433-C(O)—NH—B434, —NB435-C(O)—NB436B437,        —NHS(O₂)—B438, —NB439S(O₂)— B440, —S—B441, —S(O)—B442,        —S(O₂)—B443, —S(O₂)NH—B444, —S(O₂)NB445B446, —S(O₂)O—B447,        —P(O)(OB448)(OB449), —Si(B450)(B451)(B452), —C(NH)—NH₂,        —C(NB453)-NH₂, —C(NH)—NHB454, —C(NH)—NB455B456,        —C(NB457)-NHB458, —C(NB459)-NB460B461, —NH—C(O)—NH—O—B462,        —NH—C(O)—NB463-O—B464, —NB465-C(O)—NB466-O—B467,        —N(—C(O)—NH—O—B468)₂, —N(—C(O)—NB469-O—B470)₂,        —N(—C(O)—NH—O—B471)(—C(O)—NB472-O—B473), —C(S)—B474,        —C(S)—O—B475, —C(S)—NH—B476, —C(S)—NB477B478, —C(O)—NH—O—B479,        —C(O)—NB480-O—B481, —C(S)—NH—O—B482, —C(S)—NB483-O—B484,        —C(O)—NH—NH—B485, —C(O)—NH—NB486B487, —C(O)—NB488-NB489B490,        —C(S)—NH—NH—B491, —C(S)—NH—NB492B493, —C(S)—NB494-NB495B496,        —C(O)—C(O)—O—B497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB498,        —C(O)—C(O)—NB499B500, —C(S)—C(O)—O—B501, —C(O)—C(S)—O—B502,        —C(S)—C(S)—O—B503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB504,        —C(S)—C(O)—NB505B506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB507,        —C(S)—C(S)—NB508B509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB510,        —C(O)—C(S)—NB511B512”;        -   wherein B401, B402, B403, B404, B405, B406, B407, B408,            B409, B410, B411, B412, B413, B414, B415, B416, B417, B418,            B419, B420, B421, B422, B423, B424, B425, B426, B427, B428,            B429, B430, B431, B432, B433, B434, B435, B436, B437, B438,            B439, B440, B441, B442, B443, B444, B445, B446, B447, B448,            B449, B450, B451, B452, B453, B454, B455, B456, B457, B458,            B459, B460, B461, B462, B463, B464, B465, B466, B467, B468,            B469, B470, B471, B472, B473, B474, B475, B476, B477, B478,            B479, B480, B481, B482, B483, B484, B485, B486, B487, B488,            B489, B490, B491, B492, B493, B494, B495, B496, B497, B498,            B499, B500, B501, B502, B503, B504, B505, B506, B507, B508,            B509, B510, B511, B512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively B407, B408 and/or            B416, B417 and/or B429, B430 and/or B436, B437 and/or B445,            B446 and/or B455, B456 and/or B460, B461 and/or B477, B478            and/or B486, B487 and/or B489, B490 and/or B492, B493 and/or            B495, B496 and/or 8499, B500 and/or 8505, B506 and/or B508,            B509 and/or 8511, B512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHB601, —NB602B603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—B604, —C(O)O—B605, —C(O)NH—B606, —C(O)NB607B608, —O—B609,        —O(—B610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—B611-O)_(f)—B612 (f=1,        2, 3, 4, 5), —OC(O)—B613, —OC(O)—O—B614, —OC(O)—NHB615,        —O—C(O)—NB616B617, —OP(O)(OB618)(OB619), —OSi(B620)(B621)(B622),        —OS(O₂)—B623, —NHC(O)—NH₂, —NHC(O)—B624, —NB625C(O)—B626,        —NH—C(O)—O—B627, —NH—C(O)—NH—B628, —NH—C(O)—NB629B630,        —NB631-C(O)—O—B632, —NB633-C(O)—NH—B634, —NB635-C(O)—NB636B637,        —NHS(O₂)—B638, —NB639S(O₂)—B640, —S—B641, —S(O)—B642,        —S(O₂)—B643, —S(O₂)NH—B644, —S(O₂)NB645B646, —S(O₂)O—B647,        —P(O)(OB648)(OB649), —Si(B650)(B651)(B652), —C(NH)—NH₂,        —C(NB653)-NH₂, —C(NH)—NHB654, —C(NH)—NB655B656,        —C(NB657)-NHB658, —C(NB659)-NB660B661, —NH—C(O)—NH—O—B662,        —NH—C(O)—NB663-O—B664, —NB665-C(O)—NB666-O—B667,        —N(—C(O)—NH—O—B668)₂, —N(—C(O)—NB669-O—B670)₂,        —N(—C(O)—NH—O—B671)(—C(O)—NB672-O—B673), —C(S)—B674,        —C(S)—O—B675, —C(S)—NH—B676, —C(S)—NB677B678, —C(O)—NH—O—B679,        —C(O)—NB680-O—B681, —C(S)—NH—O—B682, —C(S)—NB683-O—B684,        —C(O)—NH—NH—B685, —C(O)—NH—NB686B687, —C(O)—NB688-NB689B690,        —C(S)—NH—NH—B691, —C(S)—NH—NB692B693, —C(S)—NB694-NB695B696,        —C(O)—C(O)—O—B697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB698,        —C(O)—C(O)—NB699B700, —C(S)—C(O)—O—B701, —C(O)—C(S)—O—B702,        —C(S)—C(S)—O—B703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB704,        —C(S)—C(O)—NB705B706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB707,        —C(S)—C(S)—NB708B709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB710,        —C(O)—C(S)—NB711B712”;        -   wherein B601, B602, B603, B604, B605, B606, B607, B608,            B609, B610, B611, B612, B613, B614, B615, B616, B617, B618,            B619, B620, B621, B622, B623, B624, B625, B626, B627, B628,            B629, B630, B631, B632, B633, B634, B635, B636, B637, B638,            B639, B640, B641, B642, B643, B644, B645, B646, B647, B648,            B649, B650, B651, B652, B653, B654, B655, B656, B657, B658,            B659, B660, B661, B662, B663, B664, B665, B666, B667, B668,            B669, B670, B671, B672, B673, B674, B675, B676, B677, B678,            B679, B680, B681, B682, B683, B684, B685, B686, B687, B688,            B689, B690, B691, B692, B693, B694, B695, B696, B697, B698,            B699, B700, B701, B702, B703, B704, B705, B706, B707, B708,            B709, 8710, B711, B712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively B607, B608 and/or            B616, B617 and/or B629, B630 and/or B636, B637 and/or B645,            and/or B686, B687 and/or 8689, B690 and/or B692, B693 and/or            B695, B696 and/or 8699, B700 and/or B705, B706 and/or 8708,            B709 and/or 8711, B712 and/or respectively together can also            form “heterocyclyl”.

The object of the present invention has surprisingly been solved in oneaspect by providing pyrido[2,3-b]pyrazine derivatives according togeneral formula (Ib)

wherein:one of radicals R3, R4 independently is selected, or both of radicalsR3, R4 independently from each other are selected from the groupconsisting of:

-   (1) “—NR6R7”;    wherein radicals R6, R7 are independently from each other selected    from the group consisting of:    (a) “hydrogen”;    -   with the first proviso that radicals R6, R7 are not both        hydrogen at the same time;    -   with the second proviso that, if one of radicals R6, R7        independently is “hydrogen”, radical R5 is not selected from the        group consisting of: “—NH-cycloalkyl, —NH-heterocyclyl,        —NH-aryl, —NH-heteroaryl, halogen, —F, —Cl, —Br, —I,        —NR_(a)R_(b)”, with Ra, Rb being independently selected from the        group consisting of: “H, alkyl, cycloalkyl, cycloalkylalkyl,        aryl, arylalkyl, heteroaryl, heteroarylalkyl, —NR_(c)R_(d)”, Rc,        Rd in turn being independently selected from the group        consisting of: “H, alkyl, cycloalkyl, cycloalkylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl”;

(b) “—C(Y1)NR8R9, —C(═NR10)-R11, —C(Y2)NR12-Y3-R13”;

-   -   wherein Y1, Y2 are independently from each other selected from        the group consisting of: “═O, ═S, ═NH, ═NR14”;    -   wherein Y3 is independently selected from the group consisting        of: “O, S”;    -   wherein radicals R8, R9, R10, R11, R12, R13, R14 are        independently from each other selected from the group consisting        of:    -   (I) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, —F, —Cl, —Br, —I, —CN,        —CF₃, —N₃, —NH₂, —NHX1, —NX2×3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH,        —O—SO₃H, —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X4, —C(O)O—X5, —C(O)NH—X6, —C(O)NX7×8, —O—X9,        —O(—X10-0)_(a)—H (a=1, 2, 3, 4, 5), —O(—X11-O)_(b)—X12 (b=1, 2,        3, 4, 5), —OC(O)—X13, —OC(O)—O—X14, —OC(O)—NHX15,        —O—C(O)—NX16×17, —OP(O)(OX18)(OX19), —OSi(X20)(X21)(X22),        —OS(O₂)—X23, —NHC(O)—NH₂, —NHC(O)—X24, —NX25C(O)—X26,        —NH—C(O)—O—X27, —NH—C(O)—NH—X28, —NH—C(O)—NX29×30,        —NX31-C(O)—O—X32, —NX33-C(O)—NH—X34, —NX35-C(O)—NX36×37,        —NHS(O₂)—X38, —NX39S(O₂)—X40, —S—X41, —S(O)—X42, —S(O₂)—X43,        —S(O₂)NH—X44, —S(O₂)NX45×46, —S(O₂)O—X47, —P(O)(OX48)(OX49),        —Si(X50)(X51)(X52), —C(NH)—NH₂, —C(NX53)-NH₂, —C(NH)—NHX54,        —C(NH)—NX55×56, —C(NX57)-NHX58, —C(NX59)-NX60×61,        —NH—C(O)—NH—O—X62, —NH—C(O)—NX63-O—X64, —NX65-C(O)—NX66-O—X67,        —N(—C(O)—NH—O—X68)₂, —N(—C(O)—NX69-O—X70)₂,        —N(—C(O)—NH—O—X71)(—C(O)—NX72-O—X73), —C(S)—X74, —C(S)—O—X75,        —C(S)—NH—X76, —C(S)—NX77×78, —C(O)—NH—O—X79, —C(O)—NX80-O—X81,        —C(S)—NH—O—X82, —C(S)—NX83-O—X84, —C(O)—NH—NH—X85,        —C(O)—NH—NX86×87, —C(O)—NX88-NX89×90, —C(S)—NH—NH—X91,        —C(S)—NH—NX92×93, —C(S)—NX94-NX95×96, —C(O)—C(O)—O—X97,        —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX98, —C(O)—C(O)—NX99×100,        —C(S)—C(O)—O—X101, —C(O)—C(S)—O—X102, —C(S)—C(S)—O—X103,        —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX104, —C(S)—C(O)—NX105X106,        —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX107, —C(S)—C(S)—NX108X109,        —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX110, —C(O)—C(S)—NX111×112”;        -   wherein X1, X2, X3, X4, X5, X6, X7, X8, X9, X10, X11, X12,            X13, X14, X15, X16, X17, X18, X19, X20, X21, X22, X23, X24,            X25, X26, X27, X28, X29, X30, X31, X32, X33, X34, X35, X36,            X37, X38, X39, X40, X41, X42, X43, X44, X45, X46, X47, X48,            X49, X50, X51, X52, X53, X54, X55, X56, X57, X58, X59, X60,            X61, X62, X63, X64, X65, X66, X67, X68, X69, X70, X71, X72,            X73, X74, X75, X76, X77, X78, X79, X80, X81, X82, X83, X84,            X85, X86, X87, X88, X89, X90, X91, X92, X93, X94, X95, X96,            X97, X98, X99, X100, X101, X102, X103, X104, X105, X106,            X107, X108, X109, X110, X111, X112 are independently from            each other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and wherein alternatively X7,            X8 and/or X16, X17 and/or X29, X30 and/or X36, X37 and/or            X45, X46 and/or X55, X56 and/or X60, X61 and/or X77, X78            and/or X86, X87 and/or X89, X90 and/or X92, X93 and/or X95,            X96 and/or X99, X100 and/or X105, X106 and/or X108, X109            and/or X111, X112 and/or respectively together can also form            “heterocyclyl”;        -   wherein optionally above substituents of substituents group            (I)—if not hydrogen—can in turn independently from each            other be substituted with at least one substituent,            identical or different, selected from the group consisting            of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHX201, —NX202×203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X204, —C(O)O—X205, —C(O)NH—X206, —C(O)NX207×208, —O—X209,        —O(—X210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(—X211-O)_(d)—X212 (d=1,        2, 3, 4, 5), —OC(O)—X213, —OC(O)—O—X214, —OC(O)—NHX215,        —O—C(O)—NX216×217, —OP(O)(OX218)(OX219), —OSi(X220)(X221)(X222),        —OS(O₂)—X223, —NHC(O)—NH₂, —NHC(O)—X224, —NX225C(O)—X226,        —NH—C(O)—O—X227, —NH—C(O)—NH—X228, —NH—C(O)—NX229×230,        —NX231-C(O)—O—X232, —NX233-C(O)—NH—X234, —NX235-C(O)—NX236×237,        —NHS(O₂)—X238, —NX239S(O₂)—X240, —S—X241, —S(O)—X242,        —S(O₂)—X243, —S(O₂)NH—X244, —S(O₂)NX245×246, —S(O₂)O—X247,        —P(O)(OX248)(OX249), —Si(X250)(X251)(X252), —C(NH)—NH₂,        —C(NX253)-NH₂, —C(NH)—NHX254, —C(NH)—NX255×256,        —C(NX257)-NHX258, —C(NX259)-NX260×261, —NH—C(O)—NH—O—X262,        —NH—C(O)—NX263-O—X264, —NX265-C(O)—NX266-O—X267,        —N(—C(O)—NH—O—X268)₂, —N(—C(O)—NX269-O—X270)₂,        —N(—C(O)—NH—O—X271)(—C(O)—NX272-O—X273), —C(S)—X274,        —C(S)—O—X275, —C(S)—NH—X276, —C(S)—NX277×278, —C(O)—NH—O—X279,        —C(O)—NX280-O—X281, —C(S)—NH—O—X282, —C(S)—NX283-O—X284,        —C(O)—NH—NH—X285, —C(O)—NH—NX286×287, —C(O)—NX288-NX289×290,        —C(S)—NH—NH—X291, —C(S)—NH—NX292×293, —C(S)—NX294-NX295×296,        —C(O)—C(O)—O—X297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX298,        —C(O)—C(O)—NX299×300, —C(S)—C(O)—O—X301, —C(O)—C(S)—O—X302,        —C(S)—C(S)—O—X303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX304,        —C(S)—C(O)—NX305×306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX307,        —C(S)—C(S)—NX308×309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX310,        —C(O)—C(S)—NX311×312”;        -   wherein X201, X202, X203, X204, X205, X206, X207, X208,            X209, X210, X211, X212, X213, X214, X215, X216, X217, X218,            X219, X220, X221, X222, X223, X224, X225, X226, X227, X228,            X229, X230, X231, X232, X233, X234, X235, X236, X237, X238,            X239, X240, X241, X242, X243, X244, X245, X246, X247, X248,            X249, X250, X251, X252, X253, X254, X255, X256, X257, X258,            X259, X260, X261, X262, X263, X264, X265, X266, X267, X268,            X269, X270, X271, X272, X273, X274, X275, X276, X277, X278,            X279, X280, X281, X282, X283, X284, X285, X286, X287, X288,            X289, X290, X291, X292, X293, X294, X295, X296, X297, X298,            X299, X300, X301, X302, X303, X304, X305, X306, X307, X308,            X309, X310, X311, X312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively X207, X208 and/or            X216, X217 and/or X229, X230 and/or X236, X237 and/or X245,            X246 and/or X255, X256 and/or X260, X261 and/or X277, X278            and/or X286, X287 and/or X289, X290 and/or X292, X293 and/or            X295, X296 and/or X299, X300 and/or X305, X306 and/or X308,            X309 and/or X311, X312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHX401, —NX402×403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X404, —C(O)O—X405, —C(O)NH—X406, —C(O)NX407×408, —O—X409,        —O(—X410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—X411-O)_(f)X412 (f=1,        2, 3, 4, 5), —OC(O)—X413, —OC(O)—O—X414, —OC(O)—NHX415,        —O—C(O)—NX416×417, —OP(O)(OX418)(OX419), —OSi(X420)(X421)(X422),        —OS(O₂)—X423, —NHC(O)—NH₂, —NHC(O)—X424, —NX425C(O)—X426,        —NH—C(O)—O—X427, —NH—C(O)—NH—X428, —NH—C(O)—NX429×430,        —NX431-C(O)—O—X432, —NX433-C(O)—NH—X434, —NX435-C(O)—NX436×437,        —NHS(O₂)—X438, —NX439S(O₂)—X440, —S—X441, —S(O)—X442,        —S(O₂)—X443, —S(O₂)NH—X444, —S(O₂)NX445×446, —S(O₂)O—X447,        —P(O)(OX448)(OX449), —Si(X450)(X451)(X452), —C(NH)—NH₂,        —C(NX453)-NH₂, —C(NH)—NHX454, —C(NH)—NX455×456,        —C(NX457)-NHX458, —C(NX459)-NX460×461, —NH—C(O)—NH—O—X462,        —NH—C(O)—NX463-O—X464, —NX465-C(O)—NX466-O—X467,        —N(—C(O)—NH—O—X468)₂, —N(—C(O)—NX469-O—X470)₂,        —N(—C(O)—NH—O—X471)(—C(O)—NX472-O—X473), —C(S)—X474,        —C(S)—O—X475, —C(S)—NH—X476, —C(S)—NX477×478, —C(O)—NH—O—X479,        —C(O)—NX480-O—X481, —C(S)—NH—O—X482, —C(S)—NX483-O—X484,        —C(O)—NH—NH—X485, —C(O)—NH—NX486×487, —C(O)—NX488-NX489×490,        —C(S)—NH—NH—X491, —C(S)—NH—NX492×493, —C(S)—NX494-NX495×496,        —C(O)—C(O)—O—X497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX498,        —C(O)—C(O)—NX499×500, —C(S)—C(O)—O—X501, —C(O)—C(S)—O—X502,        —C(S)—C(S)—O—X503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX504,        —C(S)—C(O)—NX505×506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX507,        —C(S)—C(S)—NX508×509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX510,        —C(O)—C(S)—NX511×512”;        -   wherein X401, X402, X403, X404, X405, X406, X407, X408,            X409, X410, X411, X412, X413, X414, X415, X416, X417, X418,            X419, X420, X421, X422, X423, X424, X425, X426, X427, X428,            X429, X430, X431, X432, X433, X434, X435, X436, X437, X438,            X439, X450, X451, X452, X453, X454, X455, X456, X457, X458,            X459, X460, X461, X462, X463, X464, X465, X466, X467, X468,            X469, X470, X471, X472, X473, X474, X475, X476, X477, X478,            X479, X480, X481, X482, X483, X484, X485, X486, X487, X488,            X489, X490, X491, X492, X493, X494, X495, X496, X497, X498,            X499, X500, X501, X502, X503, X504, X505, X506, X507, X508,            X509, X510, X511, X512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively X407, X408 and/or            X416, X417 and/or X429, X430 and/or X436, X437 and/or X445,            X446 and/or X455, X456 and/or X460, X461 and/or X477, X478            and/or X486, X487 and/or X489, X490 and/or X492, X493 and/or            X495, X496 and/or X499, X500 and/or X505, X506 and/or X508,            X509 and/or X511, X512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHX601, —NX602×603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—X604, —C(O)O—X605, —C(O)NH—X606, —C(O)NX607×608, —O—X609,        —O(—X610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—X611-O)₁—X612 (f=1, 2,        3, 4, 5), —OC(O)—X613, —OC(O)—O—X614, —OC(O)—NHX615,        —O—C(O)—NX616×617, —OP(O)(OX618)(OX619), —OSi(X620)(X621)(X622),        —OS(O₂)—X623, —NHC(O)—NH₂, —NHC(O)—X624, —NX625C(O)—X626,        —NH—C(O)—O—X627, —NH—C(O)—NH—X628, —NH—C(O)—NX629×630,        —NX631-C(O)—O—X632, —NX633-C(O)—NH—X634, —NX635-C(O)—NX636×637,        —NHS(O₂)—X638, —NX639S(O₂)—X640, —S—X641, —S(O)—X642, —X647,        —P(O)(OX648)(OX649), —Si(X650)(X651)(X652), —C(NH)—NH₂,        —C(NX653)-NH₂, —C(NH)—NHX654, —C(NH)—NX655×656,        —C(NX657)-NHX658, —C(NX659)-NX660×661, —NH—C(O)—NH—O—X662,        —NH—C(O)—NX663-O—X664, —NX665-C(O)—NX666-O—X667,        —N(—C(O)—NH—O—X668)₂, —N(—C(O)—NX669-O—X670)₂,        —N(—C(O)—NH—O—X671)(—C(O)—NX672-O—X673), —C(S)—X674,        —C(S)—O—X675, —C(S)—NH—X676, —C(S)—NX677×678, —C(O)—NH—O—X679,        —C(O)—NX680-O—X681, —C(S)—NH—O—X682, —C(S)—NX683-O—X684,        —C(O)—NH—NH—X685, —C(O)—NH—NX686×687, —C(O)—NX688-NX689×690,        —C(S)—NH—NH—X691, —C(S)—NH—NX692×693, —C(S)—NX694-NX695×696,        —C(O)—C(O)—O—X697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHX698,        —C(O)—C(O)—NX699×700, —C(S)—C(O)—O—X701, —C(O)—C(S)—O—X702,        —C(S)—C(S)—O—X703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHX704,        —C(S)—C(O)—NX705×706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHX707,        —C(S)—C(S)—NX708×709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHX710,        —C(O)—C(S)—NX711×712”;        -   wherein X601, X602, X603, X604, X605, X606, X607, X608,            X609, X610, X611, X612, X613, X614, X615, X616, X617, X618,            X619, X620, X621, X622, X623, X624, X625, X626, X627, X628,            X629, X630, X631, X632, X633, X634, X635, X636, X637, X638,            X639, X640, X641, X642, X643, X644, X645, X646, X647, X648,            X649, X650, X651, X652, X653, X654, X655, X656, X657, X658,            X659, X660, X661, X662, X663, X664, X665, X666, X667, X668,            X669, X670, X671, X672, X673, X674, X675, X676, X677, X678,            X679, X680, X681, X682, X683, X684, X685, X686, X687, X688,            X689, X690, X691, X692, X693, X694, X695, X696, X697, X698,            X699, X700, X701, X702, X703, X704, X705, X706, X707, X708,            X709, X710, X711, X712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively X607, X608 and/or            X616, X617 and/or X629, X630 X660, X661 and/or X677, X678            and/or X686, X687 and/or X689, X690 and/or X692, X693 and/or            X695, X696 and/or X699, X700 and/or X705, X706 and/or X708,            X709 and/or X711, X712 and/or respectively together can also            form “heterocyclyl”;    -   with the first proviso that “—C(Y1)-NR8R9” is not selected from        the group consisting of: “—C(O)—NR_(a)R_(b)”, with Ra, Rb        independently from each other being selected from the group        consisting of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, aryl, arylalkyl,        heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl”    -   with the second proviso that, if “—C(Y1)-NR8R9” independently is        selected from the group consisting of: “—C(O)—N[C(O)—O-alkyl]₂,        —C(O)—N[C(O)-alkyl]₂, —C(O)—N[S(O₂)-alkyl]₂,        —C(O)—N[S(O₂)-cycloalkyl]₂, —C(O)—N[S(O₂)—cycloalkylalkyl]₂,        —C(O)—N[S(O₂)-aryl]₂, —C(O)—N[S(O₂)-heterocyclyl]₂”, radicals        R1, R2 independently from each other are not “phenyl”;    -   with the third proviso that, if “—C(Y2)-NR12-Y3-R13”        independently is selected from the group consisting of:        “—C(O)—N[O-alkyl]₂”, radicals R1, R2 independently from each        other are not “phenyl”;

(c) “—C(O)—C(O)—R16”;

-   -   wherein radical R16 is independently selected from the group        consisting of:    -   (II) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, —F, —Cl, —Br, —I, —CN,        —CF₃, —N₃, —NH₂, —NHZ1, —NZ2Z3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH,        —O—SO₃H, —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z4, —C(O)O—Z5, —C(O)NH—Z6, —C(O)NZ7Z8, —O—Z9,        —O(—Z10-O)_(a)—H (a=1, 2, 3, 4, 5), —O(—Z11-O)_(b)—Z12 (b=1, 2,        3, 4, 5), —OC(O)—Z13, —OC(O)—O—Z14, —OC(O)—NHZ15,        —O—C(O)—NZ16Z17, —OP(O)(OZ18)(OZ19), —OSi(Z20)(Z21)(Z22),        —OS(O₂)—Z23, —NHC(O)—NH₂, —NHC(O)—Z24, —NZ25C(O)—Z26,        —NH—C(O)—O—Z27, —NH—C(O)—NH—Z28, —NH—C(O)—NZ29Z30,        —NZ31-C(O)—O—Z32, —NZ33-C(O)—NH—Z34, —NZ35-C(O)—NZ36Z37,        —NHS(O₂)—Z38, —NZ39S(O₂)—Z40, —S—Z41, —S(O)—Z42, —S(O₂)—Z43,        —S(O₂)NH—Z44, —S(O₂)NZ45Z46, —S(O₂)O—Z47, —P(O)(OZ48)(OZ49),        —Si(Z50)(Z51)(Z52), —C(NH)—NH₂, —C(NZ53)-NH₂, —C(NH)—NHZ54,        —C(NH)—NZ55Z56, —C(NZ57)-NHZ58, —C(NZ59)-NZ60Z61,        —NH—C(O)—NH—O—Z62, —NH—C(O)—NZ63-O—Z64, —NZ65-C(O)—NZ66-O—Z67,        —N(—C(O)—NH—O—Z68)₂, —N(—C(O)—NZ69-O—Z70)₂,        —N(—C(O)—NH—O—Z71)(—C(O)—NZ72-O—Z73), —C(S)—Z74, —C(S)—O—Z75,        —C(S)—NH—Z76, —C(S)—NZ77Z78, —C(O)—NH—O—Z79, —C(O)—NZ80-O—Z81,        —C(S)—NH—O—Z82, —C(S)—NZ83-O—Z84, —C(O)—NH—NH—Z85,        —C(O)—NH—NZ86Z87, —C(O)—NZ88-NZ89Z90, —C(S)—NH—NH—Z91,        —C(S)—NH—NZ92Z93, —C(S)—NZ94-NZ95Z96, —C(O)—C(O)—O—Z97,        —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ98, —C(O)—C(O)—NZ99Z100,        —C(S)—C(O)—O—Z101, —C(O)—C(S)—O—Z102, —C(S)—C(S)—O—Z103,        —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ104, —C(S)—C(O)—NZ105Z106,        —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ107, —C(S)—C(S)—NZ108Z109,        —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ110, —C(O)—C(S)—NZ111Z112”;        -   wherein Z1, Z2, Z3, Z4, Z5, Z6, Z7, Z8, Z9, Z10, Z11, Z12,            Z13, Z14, Z15, Z16, Z17, Z18, Z19, Z20, Z21, Z22, Z23, Z24,            Z25, Z26, Z27, Z28, Z29, Z30, Z31, Z32, Z33, Z34, Z35, Z36,            Z37, Z38, Z39, Z40, Z41, Z42, Z43, Z44, Z45, Z46, Z47, Z48,            Z49, Z50, Z51, Z52, Z53, Z54, Z55, Z56, Z57, Z58, Z59, Z60,            Z61, Z62, Z63, Z64, Z65, Z66, Z67, Z68, Z69, Z70, Z71, Z72,            Z73, Z74, Z75, Z76, Z77, Z78, Z79, Z80, Z81, Z82, Z83, Z84,            Z85, Z86, Z87, Z88, Z89, Z90, Z91, Z92, Z93, Z94, Z95, Z96,            Z97, Z98, Z99, Z100, Z101, Z102, Z103, Z104, Z105, Z106,            Z107, Z108, Z109, Z110, Z111, Z112 are independently from            each other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and wherein alternatively Z7,            Z8 and/or Z16, Z17 and/or Z29, Z30 and/or Z36, Z37 and/or            Z45, Z46 and/or Z55, Z56 and/or Z60, Z61 and/or Z77, Z78            and/or Z86, Z87 and/or Z89, Z90 and/or Z92, Z93 and/or Z95,            Z96 and/or Z99, Z100 and/or Z105, Z106 and/or Z108, Z109            and/or Z111, Z112 and/or respectively together can also form            “heterocyclyl”;        -   wherein optionally above substituents of substituents group            (II)—if not hydrogen—can in turn independently from each            other be substituted with at least one substituent,            identical or different, selected from the group consisting            of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclyalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHZ201, —NZ202Z203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z204, —C(O)O—Z205, —C(O)NH—Z206, —C(O)NZ207Z208, —O—Z209,        —O(—Z210-O), —H (c=1, 2, 3, 4, 5), —O(—Z211-O)_(d)—Z212 (d=1, 2,        3, 4, 5), —OC(O)—Z213, —OC(O)—O—Z214, —OC(O)—NHZ215,        —O—C(O)—NZ216Z217, —OP(O)(OZ218)(OZ219), —OSi(Z220)(Z221)(Z222),        —OS(O₂)—Z223, —NHC(O)—NH₂, —NHC(O)—Z224, —NZ225C(O)—Z226,        —NH—C(O)—O—Z227, —NH—C(O)—NH—Z228, —NH—C(O)—NZ229Z230,        —NZ231-C(O)—O—Z232, —NZ233-C(O)—NH—Z234, —NZ235-C(O)—NZ236Z237,        —NHS(O₂)—Z238, —NZ239S(O₂)—Z240, —S—Z241, —S(O)—Z242,        —S(O₂)—Z243, —S(O₂)NH—Z244, —S(O₂)NZ245Z246, —S(O₂)O—Z247,        —P(O)(OZ248)(OZ249), —Si(Z250)(Z251)(Z252), —C(NH)—NH₂,        —C(NZ253)-NH₂, —C(NH)—NHZ254, —C(NH)—NZ255Z256,        —C(NZ257)-NHZ258, —C(NZ259)-NZ260Z261, —NH—C(O)—NH—O—Z262,        —NH—C(O)—NZ263-O—Z264, —NZ265-C(O)—NZ266-O—Z267,        —N(—C(O)—NH—O—Z268)₂, —N(—C(O)—NZ269-O—Z270)₂,        —N(—C(O)—NH—O—Z271)(—C(O)—NZ272-O—Z273), —C(S)—Z274,        —C(S)—O—Z275, —C(S)—NH—Z276, —C(S)—NZ277Z278, —C(O)—NH—O—Z279,        —C(O)—NZ280-O—Z281, —C(S)—NH—O—Z282, —C(S)—NZ283-O—Z284,        —C(O)—NH—NH—Z285, —C(O)—NH—NZ286Z287, —C(O)—NZ288-NZ289Z290,        —C(S)—NH—NH—Z291, —C(S)—NH—NZ292Z293, —C(S)—NZ294-NZ295Z296,        —C(O)—C(O)—O—Z297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ298,        —C(O)—C(O)—NZ299Z300, —C(S)—C(O)—O—Z301, —C(O)—C(S)—O—Z302,        —C(S)—C(S)—O—Z303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ304,        —C(S)—C(O)—NZ305Z306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ307,        —C(S)—C(S)—NZ308Z309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ310,        —C(O)—C(S)—NZ311Z312”;        -   wherein Z201, Z202, Z203, Z204, Z205, Z206, Z207, Z208,            Z209, Z210, Z211, Z212, Z213, Z214, Z215, Z216, Z217, Z218,            Z219, Z220, Z221, Z222, Z223, Z224, Z225, Z226, Z227, Z228,            Z229, Z230, Z231, Z232, Z233, Z234, Z235, Z236, Z237, Z238,            Z239, Z240, Z241, Z242, Z243, Z244, Z245, Z246, Z247, Z248,            Z249, Z250, Z251, Z252, Z253, Z254, Z255, Z256, Z257, Z258,            Z259, Z260, Z261, Z262, Z263, Z264, Z265, Z266, Z267, Z268,            Z269, Z270, Z271, Z272, Z273, Z274, Z275, Z276, Z277, Z278,            Z279, Z280, Z281, Z282, Z283, Z284, Z285, Z286, Z287, Z288,            Z289, Z290, Z291, Z292, Z293, Z294, Z295, Z296, Z297, Z298,            Z299, Z300, Z301, Z302, Z303, Z304, Z305, Z306, Z307, Z308,            Z309, Z310, Z311, Z312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively Z207, Z208 and/or            Z216, Z217 and/or Z229, Z230 and/or Z236, Z237 and/or Z245,            Z246 and/or Z255, Z256 and/or Z260, Z261 and/or Z277, Z278            and/or Z286, Z287 and/or Z289, Z290 and/or Z292, Z293 and/or            Z295, Z296 and/or Z299, Z300 and/or Z305, Z306 and/or Z308,            Z309 and/or Z311, Z312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHZ401, —NZ402Z403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z404, —C(O)O—Z405, —C(O)NH—Z406, —C(O)NZ407Z408, —O—Z409,        —O(—Z410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—Z411-O)_(f)—Z412 (f=1,        2, 3, 4, 5), —OC(O)—Z413, —O(O)—O—Z414, —OC(O)—NHZ415,        —O—C(O)—NZ416Z417, —OP(O)(OZ418)(OZ419), —OSi(Z420)(Z421)(Z422),        —OS(O₂)—Z423, —NHC(O)—NH₂, —NHC(O)—Z424, —NZ425C(O)—Z426,        —NH—C(O)—O—Z427, —NH—C(O)—NH—Z428, —NH—C(O)—NZ429Z430,        —NZ431-C(O)—O—Z432, —NZ433-C(O)—NH—Z434, —NZ435-C(O)—NZ436Z437,        —NHS(O₂)—Z438, —NZ439S(O₂)—Z440, —S—Z441, —S(O)—Z442,        —S(O₂)—Z443, —S(O₂)NH—Z444, —S(O₂)NZ445Z446, —S(O₂)O—Z447,        —P(O)(OZ448)(OZ449), —Si(Z450)(Z451)(Z452), —C(NH)—NH₂,        —C(NZ453)-NH₂, —C(NH)—NHZ454, —C(NH)—NZ455Z456,        —C(NZ457)-NHZ458, —C(NZ459)-NZ460Z461, —NH—C(O)—NH—O—Z462,        —NH—C(O)—NZ463-O—Z464, —NZ465-C(O)—NZ466-O—Z467,        —N(—C(O)—NH—O—Z468)₂, —N(—C(O)—NZ469-O—Z470)₂,        —N(—C(O)—NH—O—Z471)(—C(O)—NZ472-O—Z473), —C(S)—Z474,        —C(S)—O—Z475, —C(S)—NH—Z476, —C(S)—NZ477Z478, —C(O)—NH—O—Z479,        —C(O)—NZ480-O—Z481, —C(S)—NH—O—Z482, —C(S)—NZ483-O—Z484,        —C(O)—NH—NH—Z485, —C(O)—NH—NZ486Z487, —C(O)—NZ488-NZ489Z490,        —C(S)—NH—NH—Z491, —C(S)—NH—NZ492Z493, —C(S)—NZ494-NZ495Z496,        —C(O)—C(O)—O—Z497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ498,        —C(O)—C(O)—NZ499Z500, —C(S)—C(O)—O—Z501, —C(O)—C(S)—O—Z502,        —C(S)—C(S)—O—Z503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ504,        —C(S)—C(O)—NZ505Z506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ507,        —C(S)—C(S)—NZ508Z509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ510,        —C(O)—C(S)—NZ511Z512”;        -   wherein Z401, Z402, Z403, Z404, Z405, Z406, Z407, Z408,            Z409, Z410, Z411, Z412, Z413, Z414, Z415, Z416, Z417, Z418,            Z419, Z420, Z421, Z422, Z423, Z424, Z425, Z426, Z427, Z428,            Z429, Z430, Z431, Z432, Z433, Z434, Z435, Z436, Z437, Z438,            Z439, Z440, Z441, Z442, Z443, Z444, Z445, Z446, Z447, Z448,            Z449, Z450, Z451, Z452, Z453, Z454, Z455, Z456, Z457, Z458,            Z459, Z460, Z461, Z462, Z463, Z464, Z465, Z466, Z467, Z468,            Z469, Z470, Z471, Z472, Z473, Z474, Z475, Z476, Z477, Z478,            Z479, Z480, Z481, Z482, Z483, Z484, Z485, Z486, Z487, Z488,            Z489, Z490, Z491, Z492, Z493, Z494, Z495, Z496, Z497, Z498,            Z499, Z500, Z501, Z502, Z503, Z504, Z505, Z506, Z507, Z508,            Z509, Z510, Z511, Z512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively Z407, Z408 and/or            Z416, Z417 and/or Z429, Z430 and/or Z436, Z437 and/or Z445,            Z446 and/or Z455, Z456 and/or Z460, Z461 and/or Z477, Z478            and/or Z486, Z487 and/or Z489, Z490 and/or Z492, Z493 and/or            Z495, Z496 and/or Z499, Z500 and/or Z505, Z506 and/or Z508,            Z509 and/or Z511, Z512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHZ601, —NZ602Z603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—Z604, —C(O)O—Z605, —C(O)NH—Z606, —C(O)NZ607Z608, —O—Z609,        —O(—Z610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—Z611-O)_(f)—Z612 (f=1,        2, 3, 4, 5), —OC(O)—Z613, —OC(O)—O—Z614, —OC(O)—NHZ615,        —O—C(O)—NZ616Z617, —OP(O)(OZ618)(OZ619), —OSi(Z620)(Z621)(Z622),        —OS(O₂)—Z623, —NHC(O)—NH₂, —NHC(O)—Z624, —NZ625C(O)—Z626,        —NH—C(O)—O—Z627, —NH—C(O)—NH—Z628, —NH—C(O)—NZ629Z630,        —NZ631-C(O)—O—Z632, —NZ633-C(O)—NH—Z634, —NZ635-C(O)—NZ636Z637,        —NHS(O₂)—Z638, —NZ639S(O₂)—Z640, —S—Z641, —S(O)—Z642,        —S(O₂)—Z643, —S(O₂)NH—Z644, —S(O₂)NZ645Z646, —S(O₂)O—Z647,        —P(O)(OZ648)(OZ649), —Si(Z650)(Z651)(Z652), —C(NH)—NH₂,        —C(NZ653)-NH₂, —C(NH)—NHZ654, —C(NH)—NZ655Z656,        —C(NZ657)-NHZ658, —C(NZ659)-NZ660Z661, —NH—C(O)—NH—O—Z662,        —NH—C(O)—NZ663-O—Z664, —NZ665-C(O)—NZ666-O—Z667,        —N(—C(O)—NH—O—Z668)₂, —N(—C(O)—NZ669-O—Z670)₂,        —N(—C(O)—NH—O—Z671)(—C(O)—NZ672-O—Z673), —C(S)—Z674,        —C(S)—O—Z675, —C(S)—NH—Z676, —C(S)—NZ677Z678, —C(O)—NH—O—Z679,        —C(O)—NZ680-O—Z681, —C(S)—NH—O—Z682, —C(S)—NZ683-O—Z684,        —C(O)—NH—NH—Z685, —C(O)—NH—NZ686Z687, —C(O)—NZ688-NZ689Z690,        —C(S)—NH—NH—Z691, —C(S)—NH—NZ692Z693, —C(S)—NZ694-NZ695Z696,        —C(O)—C(O)—O—Z697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHZ698,        —C(O)—C(O)—NZ699Z700, —C(S)—C(O)—O—Z701, —C(O)—C(S)—O—Z702,        —C(S)—C(S)—O—Z703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHZ704,        —C(S)—C(O)—NZ705Z706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHZ707,        —C(S)—C(S)—NZ708Z709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHZ710,        —C(O)—C(S)—NZ711Z712”;        -   wherein Z601, Z602, Z603, Z604, Z605, Z606, Z607, Z608,            Z609, Z610, Z611, Z612, Z613, Z614, Z615, Z616, Z617, Z618,            Z629, Z630, Z631, Z632, Z633, Z634, Z635, Z636, Z637, Z638,            Z639, Z640, Z641, Z642, Z643, Z644, Z645, Z646, Z647, Z648,            Z649, Z650, Z651, Z652, Z653, Z654, Z655, Z656, Z657, Z658,            Z659, Z660, Z661, Z662, Z663, Z664, Z665, Z666, Z667, Z668,            Z669, Z670, Z671, Z672, Z673, Z674, Z675, Z676, Z677, Z678,            Z679, Z680, Z681, Z682, Z683, Z684, Z685, Z686, Z687, Z688,            Z689, Z690, Z691, Z692, Z693, Z694, Z695, Z696, Z697, Z698,            Z699, Z700, Z701, Z702, Z703, Z704, Z705, Z706, Z707, Z708,            Z709, Z710, Z711, Z712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively Z607, Z608 and/or            Z616, Z617 and/or Z629, Z630 and/or Z636, Z637 and/or Z645,            Z646 and/or Z655, Z656 and/or Z660, Z661 and/or Z677, Z678            and/or Z686, Z687 and/or Z689, Z690 and/or Z692, Z693 and/or            Z695, Z696 and/or Z699, Z700 and/or Z705, Z706 and/or Z708,            Z709 and/or Z711, Z712 and/or respectively together can also            form “heterocyclyl”;    -   with the proviso that radical R16 is not “indol-yl”;

(d) “—S(O₂)—R18”;

-   -   wherein radical R18 is independently selected from the group        consisting of:    -   (III) “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NHW1, —NW2W3,        —NO₂, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO, —COON,        —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —C(O)—W4, —C(O)O—W5, —C(O)NH—W6,        —C(O)NW7W8, —O—W9, —O(—W10-O), —H (a=1, 2, 3, 4, 5),        —O(—W11-O)_(b)—W12 (b=1, 2, 3, 4, 5), —OC(O)—W13, —OC(O)—O—W14,        —OC(O)—NHW15, —O—C(O)—NW16W17, —OP(O)(OW18)(OW19),        —OSi(W20)(W21)(W22), —OS(O₂)—W23, —NHC(O)—NH₂, —NHC(O)—W24,        —NW25C(O)—W26, —NH—C(O)—O—W27, —NH—C(O)—NH—W28,        —NH—C(O)—NW29W30, —NW31-C(O)—O—W32, —NW33-C(O)—NH—W34,        —NW35-C(O)—NW36W37, —NHS(O₂)—W38, —NW39S(O₂)—W40, —S—W41,        —S(O)—W42, —S(O₂)—W43, —S(O₂)NH—W44, —S(O₂)NW45W46, —S(O₂)O—W47,        —P(O)(OW48)(OW49), —Si(W50)(W51)(W52), —C(NH)—NH₂, —C(NW53)-NH₂,        —C(NH)—NHW54, —C(NH)—NW55W56, —C(NW57)-NHW58, —C(NW59)-NW60W61,        —NH—C(O)—NH—O—W62, —NH—C(O)—NW63-O—W64, —NW65-C(O)—NW66-O—W67,        —N(—C(O)—NH—O—W68)₂, —N(—C(O)—NW69-O—W70)₂,        —N(—C(O)—NH—O—W71)(—C(O)—NW72-O—W73), —C(S)—W74, —C(S)—O—W75,        —C(S)—NH—W76, —C(S)—NW77W78, —C(O)—NH—O—W79, —C(O)—NW80-O—W81,        —C(S)—NH—O—W82, —C(S)—NW83-O—W84, —C(O)—NH—NH—W85,        —C(O)—NH—NW86W87, —C(O)—NW88-NW89W90, —C(S)—NH—NH—W91,        —C(S)—NH—NW92W93, —C(S)—NW94-NW95W96, —C(O)—C(O)—O—W97,        —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW98, —C(O)—C(O)—NW99W100,        —C(S)—C(O)—O—W101, —C(O)—C(S)—O—W102, —C(S)—C(S)—O—W103,        —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW104, —C(S)—C(O)—NW105W106,        —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW107, —C(S)—C(S)—NW108W109,        —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW110, —C(O)—C(S)—NW111W112”;        -   wherein W1, W2, W3, W4, W5, W6, W7, W8, W9, W10, W11, W12,            W13, W14, W15, W16, W17, W18, W19, W20, W21, W22, W23, W24,            W25, W26, W27, W28, W29, W30, W31, W32, W33, W34, W35, W36,            W37, W38, W39, W40, W41, W42, W43, W44, W45, W46, W47, W48,            W49, W50, W51, W52, W53, W54, W55, W56, W57, W58, W59, W60,            W61, W62, W63, W64, W65, W66, W67, W68, W69, W70, W71, W72,            W73, W74, W75, W76, W77, W78, W79, W80, W81, W82, W83, W84,            W85, W86, W87, W88, W89, W90, W91, W92, W93, W94, W95, W96,            W97, W98, W99, W100, W101, W102, W103, W104, W105, W106,            W107, W108, W109, W110, W111, W112 are independently from            each other selected from the group consisting of: “hydrogen,            alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,            heterocyclyl, heterocyclylalkyl, aryl, arylalkyl,            heteroaryl, heteroarylalkyl” and wherein alternatively W7,            W8 and/or W16, W17 and/or W29, W30 and/or W36, W37 and/or            W45, W46 and/or W55, W56 and/or W60, W61 and/or W77, W78            and/or W86, W87 and/or W89, W90 and/or W92, W93 and/or W95,            W96 and/or W99, W100 and/or W105, W106 and/or W108, W109            and/or W111, W112 and/or respectively together can also form            “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (III) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHW201, —NW202W203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—W204, —C(O)O—W205, —C(O)NH—W206, —C(O)NW207W208, —O—W209,        —O(—W210-O)_(c)—H (c=1, 2, 3, 4, 5), —O(—W211-O)_(d)—W212 (d=1,        2, 3, 4, 5), —OC(O)—W213, —OC(O)—O—W214, —OC(O)—NHW215,        —O—C(O)—NW216W217, —OP(O)(OW218)(OW219), —OSi(W220)(W221)(W222),        —OS(O₂)—W223, —NHC(O)—NH₂, —NHC(O)—W224, —NW225C(O)—W226,        —NH—C(O)—O—W227, —NH—C(O)—NH—W228, —NH—C(O)—NW229W230,        —NW231-C(O)—O—W232, —NW233-C(O)—NH—W234, —NW235-C(O)—NW236W237,        —NHS(O₂)—W238, —NW239S(O₂)—W240, —S—W241, —S(O)—W242,        —S(O₂)—W243, —S(O₂)NH—W244, —S(O₂)NW245W246, —S(O₂)O—W247,        —P(O)(OW248)(OW249), —Si(W250)(W251)(W252), —C(NH)—NH₂,        —C(NW253)-NH₂, —C(NH)—NHW254, —C(NH)—NW255W256,        —C(NW257)-NHW258, —C(NW259)-NW260W261, —NH—C(O)—NH—O—W262,        —NH—C(O)—NW263-O—W264, —NW265-C(O)—NW266-O—W267,        —N(—C(O)—NH—O—W268)₂, —N(—C(O)—NW269-O—W270)₂,        —N(—C(O)—NH—O—W271)(—C(O)—NW272-O—W273), —C(S)—W274,        —C(S)—O—W275, —C(S)—NH—W276, —C(S)—NW277W278, —C(O)—NH—O—W279,        —C(O)—NW280-O—W281, —C(S)—NH—O—W282, —C(S)—NW283-O—W284,        —C(O)—NH—NH—W285, —C(O)—NH—NW286W287, —C(O)—NW288-NW289W290,        —C(S)—NH—NH—W291, —C(S)—NH—NW292W293, —C(S)—NW294-NW295W296,        —C(O)—C(O)—O—W297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW298,        —C(O)—C(O)—NW299W300, —C(S)—C(O)—O—W301, —C(O)—C(S)—O—W302,        —C(S)—C(S)—O—W303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW304,        —C(S)—C(O)—NW305W306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW307,        —C(S)—C(S)—NW308W309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW310,        —C(O)—C(S)—NW311W312”;        -   wherein W201, W202, W203, W204, W205, W206, W207, W208,            W209, W210, W211, W212, W213, W214, W215, W216, W217, W218,            W219, W220, W221, W222, W223, W224, W225, W226, W227, W228,            W229, W230, W231, W232, W233, W234, W235, W236, W237, W238,            W239, W240, W241, W242, W243, W244, W245, W246, W247, W248,            W249, W250, W251, W252, W253, W254, W255, W256, W257, W258,            W259, W260, W261, W262, W263, W264, W265, W266, W267, W268,            W269, W270, W271, W272, W273, W274, W275, W276, W277, W278,            W279, W280, W281, W282, W283, W284, W285, W286, W287, W288,            W289, W290, W291, W292, W293, W294, W295, W296, W297, W298,            W299, W300, W301, W302, W303, W304, W305, W306, W307, W308,            W309, W310, W311, W312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively W207, W208 and/or            W216, W217 and/or W229, W230 and/or W236, W237 and/or W245,            W246 and/or W255, W256 and/or W260, W261 and/or W277, W278            and/or W286, W287 and/or W289, W290 and/or W292, W293 and/or            W295, W296 and/or W299, W300 and/or W305, W306 and/or W308,            W309 and/or W311, W312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHW401, —NW402W403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—W404, —C(O)O—W405, —C(O)NH—W406, —C(O)NW407W408, —O—W409,        —O(—W410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—W411-O)_(f)—W412 (f=1,        2, 3, 4, 5), —OC(O)—W413, —OC(O)—O—W414, —OC(O)—NHW415,        —O—C(O)—NW416W417, —OP(O)(OW418)(OW419), —OSi(W420)(W421)(W422),        —OS(O₂)—W423, —NHC(O)—NH₂, —NHC(O)—W424, —NW425C(O)—W426,        —NH—C(O)—O—W427, —NH—C(O)—NH—W428, —NH—C(O)—NW429W430,        —NW431-C(O)—O—W432, —NW433-C(O)—NH—W434, —NW435-C(O)—NW436W437,        —NHS(O₂)—W438, —NW439S(O₂)—W440, —S—W441, —S(O)—W442,        —S(O₂)—W443, —S(O₂)NH—W444, —S(O₂)NW445W446, —S(O₂)O—W447,        —P(O)(OW448)(OW449), —Si(W450)(W451)(W452), —C(NH)—NH₂,        —C(NW453)-NH₂, —C(NH)—NHW454, —C(NH)—NW455W456,        —C(NW457)-NHW458, —C(NW459)-NW460W461, —NH—C(O)—NH—O—W462,        —NH—C(O)—NW463-O—W464, —NW465-C(O)—NW466-O—W467,        —N(—C(O)—NH—O—W468)₂, —N(—C(O)—NW469-O—W470)₂,        —N(—C(O)—NH—O—W471)(—C(O)—NW472-O—W473), —C(S)—W474,        —C(S)—O—W475, —C(S)—NH—W476, —C(S)—NW477W478, —C(O)—NH—O—W479,        —C(O)—NW480-O—W481, —C(S)—NH—O—W482, —C(S)—NW483-O—W484,        —C(O)—NH—NH—W485, —C(O)—NH—NW486W487, —C(O)—NW488-NW489W490,        —C(S)—NH—NH—W491, —C(S)—NH—NW492W493, —C(S)—NW494-NW495W496,        —C(O)—C(O)—O—W497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHW498,        —C(O)—C(O)—NW499W500, —C(S)—C(O)—O—W501, —C(O)—C(S)—O—W502,        —C(S)—C(S)—O—W503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHW504,        —C(S)—C(O)—NW505W506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHW507,        —C(S)—C(S)—NW508W509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHW510,        —C(O)—C(S)—NW511W512”;        -   wherein W401, W402, W403, W404, W405, W406, W407, W408,            W409, W410, W411, W412, W413, W414, W415, W416, W417, W418,            W419, W420, W421, W422, W423, W424, W425, W426, W427, W428,            W429, W430, W431, W432, W433, W434, W435, W436, W437, W438,            W439, W440, W441, W442, W443, W444, W445, W446, W447, W448,            W449, W450, W451, W452, W453, W454, W455, W456, W457, W458,            W459, W460, W461, W462, W463, W464, W465, W466, W467, W468,            W469, W470, W471, W472, W473, W474, W475, W476, W477, W478,            W479, W480, W481, W482, W483, W484, W485, W486, W487, W488,            W489, W490, W491, W492, W493, W494, W495, W496, W497, W498,            W499, W500, W501, W502, W503, W504, W505, W506, W507, W508,            W509, W510, W511, W512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively W407, W408 and/or            W416, W417 and/or W429, W430 and/or W436, W437 and/or W445,            W446 and/or W455, W456 and/or W460, W461 W492, W493 and/or            W495, W496 and/or W499, W500 and/or W505, W506 and/or W508,            W509 and/or W511, W512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHW601, —NW602W603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—W604, —C(O)O—W605, —C(O)NH—W606, —C(O)NW607W608, —O—W609,        —O(—W610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—W611-O)_(f)—W612 (f=1,        2, 3, 4, 5), —OC(O)—W613, —OC(O)—O—W614, —OC(O)—NHW615,        —O—C(O)—NW616W617, —OP(O)(OW618)(OW619), —OSKW620)(W621)(W622),        —OS(O₂)—W623, —NHC(O)—NH₂, —NHC(O)—W624, —NW625C(O)—W626,        —NH—C(O)—O—W627, —NH—C(O)—NH—W628, —NH—C(O)—NW629W630,        —NW631-C(O)—O—W632, —NW633-C(O)—NH—W634, —NW635-C(O)—NW636W637,        —NHS(O₂)—W638, —NW639S(O₂)—W640, —S—W641, —S(O)—W642,        —S(O₂)—W643, —S(O₂)NH—W644, —S(O₂)NW645W646, —S(O₂)O—W647,        —P(O)(OW648)(OW649), —Si(W650)(W651)(W652), —C(NH)—NH₂,        —C(NW653)-NH₂, —C(NH)—NHW654, —C(NH)—NW655W656,        —C(NW657)-NHW658, —C(NW659)-NW660W661, —NH—C(O)—NH—O—W662,        —NH—C(O)—NW663-O—W664, —NW665-C(O)—NW666-O—W667,        —N(—C(O)—NH—O—W668)₂, —N(—C(O)—NW669-O—W670)₂,        —N(—C(O)—NH—O—W671)(—C(O)—NW672-O—W673), —C(S)—W674,        —C(S)—O—W675, —C(S)—NH—W676, —C(S)—NW677W678, —C(O)—NH—O—W679,        —C(O)—NW680-O—W681, —C(S)—NH—O—W682, —C(S)—NW683-O—W684,        —C(O)—NH—NH—W685, —C(O)—NH—NW686W687, —C(O)—NW688-NW689W690,        —C(S)—NH—NH—W691, —C(S)—NH—NW692W693, C(O)—NH₂,        —C(O)—C(O)—NHW698, —C(O)—C(O)—NW699W700, —C(S)—C(O)—O—W701,        —C(O)—C(S)—O—W702, —C(S)—C(S)—O—W703, —C(S)—C(O)—NH₂,        —C(S)—C(O)—NHW704, —C(S)—C(O)—NW705W706, —C(S)—C(S)—NH₂,        —C(S)—C(S)—NHW707, —C(S)—C(S)—NW708W709, —C(O)—C(S)—NH₂,        —C(O)—C(S)—NHW710, —C(O)—C(S)—NW711W712”;        -   wherein W601, W602, W603, W604, W605, W606, W607, W608,            W609, W610, W611, W612, W613, W614, W615, W616, W617, W618,            W619, W620, W621, W622, W623, W624, W625, W626, W627, W628,            W629, W630, W631, W632, W633, W634, W635, W636, W637, W638,            W639, W640, W641, W642, W643, W644, W645, W646, W647, W648,            W649, W650, W651, W652, W653, W654, W655, W656, W657, W658,            W659, W660, W661, W662, W663, W664, W665, W666, W667, W668,            W669, W670, W671, W672, W673, W674, W675, W676, W677, W678,            W679, W680, W681, W682, W683, W684, W685, W686, W687, W688,            W689, W690, W691, W692, W693, W694, W695, W696, W697, W698,            W699, W700, W701, W702, W703, W704, W705, W706, W707, W708,            W709, W710, W711, W712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively W607, W608 and/or            W616, W617 and/or W629, W630 and/or W636, W637 and/or W645,            W646 and/or W655, W656 and/or W660, W661 and/or W677, W678            and/or W686, W687 and/or W689, W690 and/or W692, W693 and/or            W695, W696 and/or W699, W700 and/or W705, W706 and/or W708,            W709 and/or W711, W712 and/or respectively together can also            form “heterocyclyl”;    -   with the first proviso that radical R18 is not selected from the        group consisting of: “−O-alkyl, —O—(C₉-C₃₀)alkyl, —O-aryl,        —O-arylalkyl, —O-heteroaryl, —O-heteroarylalkyl, —O-cycloalkyl,        —O-cycloalkylalkyl, —O-heterocyclyl, —O-heterocyclylalkyl”;    -   with the second proviso that, if radical R18 independently is        selected from the group consisting of: “—NR_(a)R_(b)”, with Ra,        Rb independently from each other being selected from the group        consisting of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, aryl, arylalkyl,        heteroaryl, heteroarylalkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl”, radical R1 is not selected        from the group consisting of: “heterocyclylalkyl being        substituted with ═O, where heterocyclyl is 5-membered; alkyl        being substituted with heterocyclyl, where heterocyclyl is        5-membered and substituted with ═O”;        and one of radicals R3, R4 or neither of radicals R3, R4        independently is selected from the group consisting of:

-   (2) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,    heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,    heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NHA1,    —NA2A3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO,    —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —C(O)-A4, —C(O)O-A5, —C(O)NH-A6,    —C(O)NA7A8, —O-A9, —O(-A10-O)_(a)—H (a=1, 2, 3, 4, 5),    —O(-A11-O)_(b)-A12 (b=1, 2, 3, 4, 5), —OC(O)-A13, —OC(O)—O-A14,    —OC(O)—NHA15, —O—C(O)—NA16A17, —OP(O)(OA18)(OA19),    —OSi(A20)(A21)(A22), —OS(O₂)-A23, —NHC(O)—NH₂, —NHC(O)-A24,    —NA25C(O)-A26, —NH—C(O)—O-A27, —NH—C(O)—NH-A28, —NH—C(O)—NA29A30,    —NA31-C(O)—O-A32, —NA33-C(O)—NH-A34, —NA35-C(O)—NA36A37,    —NHS(O₂)-A38, —NA39S(O₂)-A40, —S-A41, —S(O)-A42, —S(O₂)— A43,    —S(O₂)NH-A44, —S(O₂)NA45A46, —S(O₂)O-A47, —P(O)(OA48)(OA49),    —Si(A50)(A51)(A52), —C(NH)—NH₂, —C(NA53)-NH₂, —C(NH)—NHA54,    —C(NH)—NA55A56, —C(NA57)-NHA58, —C(NA59)-NA60A61, —NH—C(O)—NH—O-A62,    —NH—C(O)—NA63-O-A64, —NA65-C(O)—NA66-O-A67, —N(—C(O)—NH—O-A68)₂,    —N(—C(O)—NA69-O-A70)₂, —N(—C(O)—NH—O-A71)(—C(O)—NA72-O-A73),    —C(S)-A74, —C(S)—O-A75, —C(S)—NH-A76, —C(S)—NA77A78, —C(O)—NH—O-A79,    —C(O)—NA80-O-A81, —C(S)—NH—O-A82, —C(S)—NA83-O-A84, —C(O)—NH—NH-A85,    —C(O)—NH—NA86A87, —C(O)—NA88-NA89A90, —C(S)—NH—NH-A91,    —C(S)—NH—NA92A93, —C(S)—NA94-NA95A96, —C(O)—C(O)—O-A97,    —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA98, —C(O)—C(O)—NA99A100,    —C(S)—C(O)—O-A101, —C(O)—C(S)—O-A102, —C(S)—C(S)—O-A103,    —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA104, —C(S)—C(O)—NA105A106,    —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA107, —C(S)—C(S)—NA108A109,    —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA110, —C(O)—C(S)—NA111A112”;    -   wherein A1, A2, A3, A4, A5, A6, A7, A8, A9, A10, A11, A12, A13,        A14, A15, A16, A17, A18, A19, A20, A21, A22, A23, A24, A25, A26,        A27, A28, A29, A30, A31, A32, A33, A34, A35, A36, A37, A38, A39,        A40, A41, A42, A43, A44, A45, A46, A47, A48, A49, A50, A51, A52,        A53, A54, A55, A56, A57, A58, A59, A60, A61, A62, A63, A64, A65,        A66, A67, A68, A69, A70, A71, A72, A73, A74, A75, A76, A77, A78,        A79, A80, A81, A82, A83, A84, A85, A86, A87, A88, A89, A90, A91,        A92, A93, A94, A95, A96, A97, A98, A99, A100, A101, A102, A103,        A104, A105, A106, A107, A108, A109, A110, A111, A112 are        independently from each other selected from the group consisting        of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl” and wherein        alternatively A7, A8 and/or A16, A17 and/or A29, A30 and/or A36,        A37 and/or A45, A46 and/or A55, A56 and/or A60, A61 and/or A77,        A78 and/or A86, A87 and/or A89, A90 and/or A92, A93 and/or A95,        A96 and/or A99, A100 and/or A105, A106 and/or A108, A109 and/or        A111, A112 and/or respectively together can also form        “heterocyclyl”;    -   wherein optionally above substituents of substituents group        (2)—if not hydrogenn—can in turn independently from each other        be substituted with at least one substituent, identical or        different, selected from the group consisting of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHA201, —NA202A203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)-A204, —C(O)O-A205, —C(O)NH-A206, —C(O)NA207A208, —O-A209,        —O(-A210-O), —H (c=1, 2, 3, 4, 5), —O(-A211-O)_(d)-A212 (d=1, 2,        3, 4, 5), —OC(O)-A213, —OC(O)—O-A214, —OC(O)—NHA215,        —O—C(O)—NA216A217, —OP(O)(OA218)(OA219), —OSi        (A220)(A221)(A222), —OS(O₂)— A223, —NHC(O)—NH₂, —NHC(O)-A224,        —NA225C(O)-A226, —NH—C(O)—O-A227, —NH—C(O)—NH-A228,        —NH—C(O)—NA229A230, —NA231-C(O)—O-A232, —NA233-C(O)—NH-A234,        —NA235-C(O)—NA236A237, —NHS(O₂)— A238, —NA239S(O₂)-A240,        —S-A241, —S(O)-A242, —S(O₂)-A243, —S(O₂)NH-A244,        —S(O₂)NA245A246, —S(O₂)O-A247, —P(O)(OA248)(OA249),        —Si(A250)(A251)(A252), —C(NH)—NH₂, —C(NA253)-NH₂, —C(NH)—NHA254,        —C(NH)—NA255A256, —C(NA257)-NHA258, —C(NA259)-NA260A261,        —NH—C(O)—NH—O-A262, —NH—C(O)—NA263-O-A264,        —NA265-C(O)—NA266-O-A267, —N(—C(O)—NH—O-A268)₂,        —N(—C(O)—NA269-O-A270)₂,        —N(—C(O)—NH—O-A271)(—C(O)—NA272-O-A273), —C(S)-A274,        —C(S)—O-A275, —C(S)—NH-A276, —C(S)—NA277A278, —C(O)—NH—O-A279,        —C(O)—NA280-O-A281, —C(S)—NH—O-A282, —C(S)—NA283-O-A284,        —C(O)—NH—NH-A285, —C(O)—NH—NA286A287, —C(O)—NA288-NA289A290,        —C(S)—NH—NH-A291, —C(S)—NH—NA292A293, —C(S)—NA294-NA295A296,        —C(O)—C(O)—O-A297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA298,        —C(O)—C(O)—NA299A300, —C(S)—C(O)—O-A301, —C(O)—C(S)—O-A302,        —C(S)—C(S)—O-A303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA304,        —C(S)—C(O)—NA305A306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA307,        —C(S)—C(S)—NA308A309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA310,        —C(O)—C(S)—NA311A312”;        -   wherein A201, A202, A203, A204, A205, A206, A207, A208,            A209, A210, A211, A212, A213, A214, A215, A216, A217, A218,            A219, A220, A221, A222, A223, A224, A225, A226, A227, A228,            A229, A230, A231, A232, A233, A234, A235, A236, A237, A238,            A239, A240, A241, A242, A243, A244, A245, A246, A247, A248,            A249, A250, A251, A252, A253, A254, A255, A256, A257, A258,            A259, A260, A261, A262, A263, A264, A265, A266, A267, A268,            A269, A270, A271, A272, A273, A274, A275, A276, A277, A278,            A279, A280, A281, A282, A283, A284, A285, A286, A287, A288,            A289, A290, A291, A292, A293, A294, A295, A296, A297, A298,            A299, A300, A301, A302, A303, A304, A305, A306, A307, A308,            A309, A310, A311, A312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively A207, A208 and/or            A216, A217 and/or A229, A230 and/or A236, A237 and/or A245,            A246 and/or A255, A256 and/or A260, A261 and/or A277, A278            and/or A286, A287 and/or A289, A290 and/or A292, A293 and/or            A295, A296 and/or A299, A300 and/or A305, A306 and/or A308,            A309 and/or A311, A312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHA401, —NA402A403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)-A404, —C(O)O-A405, —C(O)NH-A406, —C(O)NA407A408, —O-A409,        —O(-A410-O)_(e)—H (e=1, 2, 3, 4, 5), —O(-A411-O)_(f)-A412 (f=1,        2, 3, 4, 5), —OC(O)-A413, —OC(O)—O-A414, —OC(O)—NHA415,        —O—C(O)—NA416A417, —OP(O)(OA418)(OA419), —OSi(A420)(A421)(A422),        —OS(O₂)-A423, —NHC(O)—NH₂, —NHC(O)-A424, —NA425C(O)-A426,        —NH—C(O)—O-A427, —NH—C(O)—NH-A428, —NH—C(O)—NA429A430,        —NA431-C(O)—O-A432, —NA433-C(O)—NH-A434, —NA435-C(O)—NA436A437,        —NHS(O₂)-A438, —NA439S(O₂)— A440, —S-A441, —S(O)-A442,        —S(O₂)-A443, —S(O₂)NH-A444, —S(O₂)NA445A446, —S(O₂)O-A447,        —P(O)(OA448)(OA449), —Si(A450)(A451)(A452), —C(NH)—NH₂,        —C(NA453)-NH₂, —C(NH)—NHA454, —C(NH)—NA455A456,        —C(NA457)-NHA458, —C(NA459)-NA460A461, —NH—C(O)—NH—O-A462,        —NH—C(O)—NA463-O-A464, —NA465-C(O)—NA466-O-A467,        —N(—C(O)—NH—O-A468)₂, —N(—C(O)—NA469-O-A470)₂,        —N(—C(O)—NH—O-A471)(—C(O)—NA472-O-A473), —C(S)-A474,        —C(S)—O-A475, —C(S)—NH-A476, —C(S)—NA477A478, —C(O)—NH—O-A479,        —C(O)—NA480-O-A481, —C(S)—NH—O-A482, —C(S)—NA483-O-A484,        —C(O)—NH—NH-A485, —C(O)—NH—NA486A487, —C(O)—NA488-NA489A490,        —C(S)—NH—NH-A491, —C(S)—NH—NA492A493, —C(S)—NA494-NA495A496,        —C(O)—C(O)—O-A497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA498,        —C(O)—C(O)—NA499A500, —C(S)—C(O)—O-A501, —C(O)—C(S)—O-A502,        —C(S)—C(S)—O-A503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA504,        —C(S)—C(O)—NA505A506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA507,        —C(S)—C(S)—NA508A509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA510,        —C(O)—C(S)—NA511A512”;        -   wherein A401, A402, A403, A404, A405, A406, A407, A408,            A409, A410, A411, A412, A413, A414, A415, A416, A417, A418,            A419, A420, A421, A422, A423, A424, A425, A426, A427, A428,            A429, A430, A431, A432, A433, A434, A435, A436, A437, A438,            A439, A440, A441, A442, A443, A444, A445, A446, A447, A448,            A449, A450, A451, A452, A453, A454, A455, A456, A457, A458,            A459, A460, A461, A462, A463, A464, A465, A466, A467, A468,            A469, A470, A471, A472, A473, A474, A475, A476, A477, A478,            A479, A480, A481, A482, A483, A484, A485, A486, A487, A488,            A489, A490, A491, A492, A493, A494, A495, A496, A497, A498,            A499, A500, A501, A502, A503, A504, A505, A506, A507, A508,            A509, A510, A511, A512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively A407, A408 and/or            A416, A417 and/or A429, A430 and/or A436, A437 and/or A445,            A446 and/or A455, A456 and/or A460, A461 and/or A477, A478            and/or A486, A487 and/or A489, A490 and/or A492, A493 and/or            A495, A496 and/or A499, A500 and/or A505, A506 and/or A508,            A509 and/or A511, A512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHA601, —NA602A603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)-A604, —C(O)O-A605, —C(O)NH-A606, —C(O)NA607A608, —O-A609,        —O(-A610-O), —H (e=1, 2, 3, 4, 5), —O(-A611-O)_(f)-A612 (f=1, 2,        3, 4, 5), —OC(O)-A613, —OC(O)—O-A614, —OC(O)—NHA615,        —O—C(O)—NA616A617, —OP(O)(OA618)(OA619), —OSi(A620)(A621)(A622),        —OS(O₂)-A623, —NHC(O)—NH₂, —NHC(O)-A624, —NA625C(O)-A626,        —NH—C(O)—O-A627, —NH—C(O)—NH-A628, —NH—C(O)—NA629A630,        —NA631-C(O)—O-A632, —NA633-C(O)—NH-A634, —NA635-C(O)—NA636A637,        —NHS(O₂)-A638, —NA639S(O₂)-A640, —S-A641, —S(O)-A642,        —S(O₂)-A643, —S(O₂)NH-A644, —S(O₂)NA645A646, —S(O₂)O-A647,        —P(O)(OA648)(OA649), —Si(A650)(A651)(A652), —C(NH)—NH₂,        —C(NA653)-NH₂, —C(NH)—NHA654, —C(NH)—NA655A656,        —C(NA657)-NHA658, —C(NA659)-NA660A661, —NH—C(O)—NH—O-A662,        —NH—C(O)—NA663-O-A664, —NA665-C(O)—NA666-O-A667,        —N(—C(O)—NH—O-A668)₂, —N(—C(O)—NA669-O-A670)₂,        —N(—C(O)—NH—O-A671)(—C(O)—NA672-O-A673), —C(S)-A674,        —C(S)—O-A675, —C(S)—NH-A676, —C(S)—NA677A678, —C(O)—NH—O-A679,        —C(O)—NA680-O-A681, —C(S)—NH—O-A682, —C(S)—NA683-O-A684,        —C(O)—NH—NH-A685, —C(O)—NH—NA686A687, —C(O)—NA688-NA689A690,        —C(S)—NH—NH-A691, —C(S)—NH—NA692A693, —C(S)—NA694-NA695A696,        —C(O)—C(O)—O-A697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHA698,        —C(O)—C(O)—NA699A700, —C(S)—C(O)—O-A701, —C(O)—C(S)—O-A702,        —C(S)—C(S)—O-A703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHA704,        —C(S)—C(O)—NA705A706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHA707,        —C(S)—C(S)—NA708A709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHA710,        —C(O)—C(S)—NA711A712”;        -   wherein A601, A602, A603, A604, A605, A606, A607, A608,            A609, A610, A611, A612, A613, A614, A615, A616, A617, A618,            A619, A620, A621, A622, A623, A624, A625, A626, A627, A628,            A629, A630, A631, A632, A633, A634, A635, A636, A637, A638,            A639, A640, A641, A642, A643, A644, A645, A646, A647, A648,            A649, A650, A651, A652, A653, A654, A655, A656, A657, A658,            A659, A660, A661, A662, A663, A664, A665, A666, A667, A668,            A669, A670, A671, A672, A673, A674, A675, A676, A677, A678,            A679, A680, A681, A682, A683, A684, A685, A686, A687, A688,            A689, A690, A691, A692, A693, A694, A695, A696, A697, A698,            A699, A700, A701, A702, A703, A704, A705, A706, A707, A708,            A709, A710, A711, A712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively A607, A608 and/or            A616, A617 and/or A629, A630 and/or A636, A637 and/or A645,            A646 and/or A655, A656 and/or A660, A661 and/or A677, A678            and/or A686, A687 and/or A689, A690 and/or A692, A693 and/or            A695, A696 and/or A699, A700 and/or A705, A706 and/or A708,            A709 and/or A711, A712 and/or respectively together can also            form “heterocyclyl”;            and radicals R1, R2, R5 independently from each other are            selected from the group consisting of:

-   (3) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,    heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,    heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NHB1,    —NB2B3, —NO₂, —OH, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO,    —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —C(O)—B4, —C(O)O—B5, —C(O)NH—B6,    —C(O)NB7B8, —O—B9, —O(—B10-O)_(a)—H (a=1, 2, 3, 4, 5),    —O(—B11-O)_(b)—B12 (b=1, 2, 3, 4, 5), —OC(O)—B13, —OC(O)—O—B14,    —OC(O)—NHB15, —O—C(O)—NB16B17, —OP(O)(OB18)(OB19),    —OSi(B20)(B21)(B22), —OS(O₂)—B23, —NHC(O)—NH₂, —NHC(O)—B24,    —NB25C(O)—B26, —NH—C(O)—O—B27, —NH—C(O)—NH—B28, —NH—C(O)—NB29B30,    —NB31-C(O)—O—B32, —NB33-C(O)—NH—B34, —NB35-C(O)—NB36B37,    —NHS(O₂)—B38, —NB39S(O₂)—B40, —S—B41, —S(O)—B42, —S(O₂)— B43,    —S(O₂)NH—B44, —S(O₂)NB45B46, —S(O₂)O—B47, —P(O)(OB48)(OB49),    —Si(B50)(B51)(B52), —C(NH)—NH₂, —C(NB53)-NH₂, —C(NH)—NHB54,    —C(NH)—NB55B56, —C(NB57)-NHB58, —C(NB59)-NB60B61, —NH—C(O)—NH—O—B62,    —NH—C(O)—NB63-O—B64, —NB65-C(O)—NB66-O—B67, —N(—C(O)—NH—O—B68)₂,    —N(—C(O)—NB69-O—B70)₂, —N(—C(O)—NH—O—B71)(—C(O)—NB72-O—B73),    —C(S)—B74, —C(S)—O—B75, —C(S)—NH—B76, —C(S)—NB77B78, —C(O)—NH—O—B79,    —C(O)—NB80-O—B81, —C(S)—NH—O—B82, —C(S)—NB83-O—B84, —C(O)—NH—NH—B85,    —C(O)—NH—NB86B87, —C(O)—NB88-NB89B90, —C(S)—NH—NH—B91,    —C(S)—NH—NB92B93, —C(S)—NB94-NB95B96, —C(O)—C(O)—O—B97,    —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB98, —C(O)—C(O)—NB99B100,    —C(S)—C(O)—O—B101, —C(O)—C(S)—O—B102, —C(S)—C(S)—O—B103,    —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB104, —C(S)—C(O)—NB105B106,    —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB107, —C(S)—C(S)—NB108B109,    —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB110, —C(O)—C(S)—NB111B112”;    -   wherein B1, B2, B3, B4, B5, B6, B7, B8, B9, B10, B11, B12, B13,        B14, B15, B16, B17, B18, B19, B20, B21, B22, B23, B24, B25, B26,        B27, B28, B29, B30, B31, B32, B33, B34, B35, B36, B37, B38, B39,        B40, B41, B42, B43, B44, B45, B46, B47, B48, B49, B50, B51, B52,        B53, B54, B55, B56, B57, B58, B59, B60, B61, B62, B63, B64, B65,        B66, B67, B68, B69, B70, B71, B72, B73, B74, B75, B76, B77, B78,        B79, B80, B81, B82, B83, B84, B85, B86, B87, B88, B89, B90, B91,        B92, B93, B94, B95, B96, B97, B98, B99, B100, B101, B102, B103,        B104, B105, B106, B107, B108, B109, B110, B111, B112 are        independently from each other selected from the group consisting        of: “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl” and wherein        alternatively B2, B3 and/or B7, B8 and/or B16, B17 and/or B29,        B30 and/or B36, B37 and/or B45, B46 and/or B55, B56 and/or B60,        B61 and/or B77, B78 and/or B86, B87 and/or B89, B90 and/or B92,        B93 and/or B95, B96 and/or B99, B100 and/or B105, B106 and/or        B108, B109 and/or B111, B112 and/or respectively together can        also form “heterocyclyl”;    -   wherein optionally above substituents of substituents group        (3)—if not hydrogen—can in turn independently from each other be        substituted with at least one substituent, identical or        different, selected from the group consisting of:    -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHB201, —NB202B203, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—B204, —C(O)O—B205, —C(O)NH—B206, —C(O)NB207B208, —O—B209,        —O(—B210-O), —H (c=1, 2, 3, 4, 5), —O(—B211-O)_(d)—B212 (d=1, 2,        3, 4, 5), —OC(O)—B213, —OC(O)—O—B214, —OC(O)—NHB215,        —O—C(O)—NB216B217, —OP(O)(OB218)(OB219), —OSi(B220)(B221)(B222),        —OS(O₂)— B223, —NHC(O)—NH₂, —NHC(O)—B224, —NB225C(O)—B226,        —NH—C(O)—O—B227, —NH—C(O)—NH—B228, —NH—C(O)—NB229B230,        —NB231-C(O)—O—B232, —NB233-C(O)—NH—B234, —NB235-C(O)—NB236B237,        —NHS(O₂)— B238, —NB239S(O₂)—B240, —S—B241, —S(O)—B242,        —S(O₂)—B243, —S(O₂)NH—B244, —S(O₂)NB245B246, —S(O₂)O—B247,        —P(O)(OB248)(OB249), —Si(B250)(B251)(B252), —C(NH)—NH₂,        —C(NB253)-NH₂, —C(NH)—NHB254, —C(NH)—NB255B256,        —C(NB257)-NHB258, —C(NB259)-NB260B261, —NH—C(O)—NH—O—B262,        —NH—C(O)—NB263-O—B264, —NB265-C(O)—NB266-O—B267,        —N(—C(O)—NH—O—B268)₂, —N(—C(O)—NB269-O—B270)₂,        —N(—C(O)—NH—O—B271)(—C(O)—NB272-O—B273), —C(S)—B274,        —C(S)—O—B275, —C(S)—NH—B276, —C(S)—NB277B278, —C(O)—NH—O—B279,        —C(O)—NB280-O—B281, —C(S)—NH—O—B282, —C(S)—NB283-O—B284,        —C(O)—NH—NH—B285, —C(O)—NH—NB286B287, —C(O)—NB288-NB289B290,        —C(S)—NH—NH—B291, —C(S)—NH—NB292B293, —C(S)—NB294-NB295B296,        —C(O)—C(O)—O—B297, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB298,        —C(O)—C(O)—NB299B300, —C(S)—C(O)—O—B301, —C(O)—C(S)—O—B302,        —C(S)—C(S)—O—B303, —C(S)—C(O)—NH₂, —C(S)—C(O)—NH B304,        —C(S)—C(O)—NB305B306, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB307,        —C(S)—C(S)—NB308B309, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB310,        —C(O)—C(S)—NB311B312”;        -   wherein 8201, B202, B203, B204, B205, B206, B207, B208,            B209, B210, 8211, B212, B213, B214, B215, B216, B217, B218,            B219, B220, B221, B222, B223, B224, B225, B226, B227, B228,            B229, B230, B231, B232, B233, B234, B235, B236, B237, B238,            B239, B240, B241, B242, B243, B244, B245, B246, B247, B248,            B249, B250, B251, B252, B253, B254, B255, B256, B257, B258,            B259, B260, B261, B262, B263, B264, B265, B266, B267, B268,            B269, B270, B271, B272, B273, B274, B275, B276, B277, B278,            B279, B280, B281, B282, B283, B284, B285, B286, B287, B288,            B289, B290, B291, B292, B293, B294, B295, B296, B297, B298,            B299, B300, B301, B302, B303, B304, B305, B306, B307, B308,            B309, 8310, B311, B312 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively 8207, B208 and/or            8216, B217 and/or 8229, B230 and/or 8236, B237 and/or B245,            B246 and/or 8255, B256 and/or B260, B261 and/or B277, B278            and/or 8286, B287 and/or 8289, B290 and/or B292, B293 and/or            B295, B296 and/or 8299, B300 and/or B305, B306 and/or B308,            B309 and/or B311, B312 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (i) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (ii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHB401, —NB402B403, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—B404, —C(O)O—B405, —C(O)NH—B406, —C(O)NB407B408, —O—B409,        —O(—B410-O), —H (e=1, 2, 3, 4, 5), —O(—B411-O)_(f)—B412 (f=1, 2,        3, 4, 5), —OC(O)—B413, —OC(O)—O—B414, —OC(O)—NHB415,        —O—C(O)—NB416B417, —OP(O)(OB418)(OB419), —OSi(B420)(B421)(B422),        —OS(O₂)—B423, —NHC(O)—NH₂, —NHC(O)—B424, —NB425C(O)—B426,        —NH—C(O)—O—B427, —NH—C(O)—NH—B428, —NH—C(O)—NB429B430,        —NB431-C(O)—O—B432, —NB433-C(O)—NH—B434, —NB435-C(O)—NB436B437,        —NHS(O₂)—B438, —NB439S(O₂)— B440, —S—B441, —S(O)—B442,        —S(O₂)—B443, —S(O₂)NH—B444, —S(O₂)NB445B446, —S(O₂)O—B447,        —P(O)(OB448)(OB449), —Si(B450)(B451)(B452), —C(NH)—NH₂,        —C(NB453)-NH₂, —C(NH)—NHB454, —C(NH)—NB455B456,        —C(NB457)-NHB458, —C(NB459)-NB460B461, —NH—C(O)—NH—O—B462,        —NH—C(O)—NB463-O—B464, —NB465-C(O)—NB466-O—B467,        —N(—C(O)—NH—O—B468)₂, —N(—C(O)—NB469-O—B470)₂,        —N(—C(O)—NH—O—B471)(—C(O)—NB472-O—B473), —C(S)—B474,        —C(S)—O—B475, —C(S)—NH—B476, —C(S)—NB477B478, —C(O)—NH—O—B479,        —C(O)—NB480-O—B481, —C(S)—NH—O—B482, —C(S)—NB483-O—B484,        —C(O)—NH—NH—B485, —C(O)—NH—NB486B487, —C(O)—NB488-NB489B490,        —C(S)—NH—NH—B491, —C(S)—NH—NB492B493, —C(S)—NB494-NB495B496,        —C(O)—C(O)—O—B497, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB498,        —C(O)—C(O)—NB499B500, —C(S)—C(O)—O—B501, —C(O)—C(S)—O—B502,        —C(S)—C(S)—O—B503, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB504,        —C(S)—C(O)—NB505B506, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB507,        —C(S)—C(S)—NB508B509, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB510,        —C(O)—C(S)—NB511B512”;        -   wherein B401, B402, B403, B404, B405, B406, B407, B408,            B409, B410, B411, B412, B413, B414, B415, B416, B417, B418,            B419, B420, B421, B422, B423, B424, B425, B426, B427, B428,            B429, B430, B431, B432, B433, B434, B435, B436, B437, B438,            B439, B440, B441, B442, B443, B444, B445, B446, B447, B448,            B449, B450, B451, B452, B453, B454, B455, B456, B457, B458,            B459, B460, B461, B462, B463, B464, B465, B466, B467, B468,            B469, B470, B471, B472, B473, B474, B475, B476, B477, B478,            B479, B480, B481, B482, B483, B484, B485, B486, B487, B488,            B489, B490, B491, B492, B493, B494, B495, B496, B497, B498,            B499, B500, B501, B502, B503, B504, B505, B506, B507, B508,            B509, B510, B511, B512 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively B407, B408 and/or            B416, B417 and/or 8429, B430 and/or 8436, B437 and/or B445,            B446 and/or B455, B456 and/or B460, B461 and/or B477, B478            and/or B486, B487 and/or 8489, B490 and/or 8492, B493 and/or            B495, B496 and/or B499, B500 and/or B505, B506 and/or B508,            B509 and/or B511, B512 and/or respectively together can also            form “heterocyclyl”;        -   wherein optionally above substituents of substituents            group (ii) can in turn independently from each other be            substituted with at least one substituent, identical or            different, selected from the group consisting of:    -   (iii) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl,        heterocyclyl, heterocyclylalkyl, aryl, arylalkyl, heteroaryl,        heteroarylalkyl, —F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NHB601, —NB602B603, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,        —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,        —C(O)—B604, —C(O)O—B605, —C(O)NH—B606, —C(O)NB607B608, —O—B609,        —O(—B610-O)_(e)—H (e=1, 2, 3, 4, 5), —O(—B611-O)_(f)—B612 (f=1,        2, 3, 4, 5), —OC(O)—B613, —OC(O)—O—B614, —OC(O)—NHB615,        —O—C(O)—NB616B617, —OP(O)(OB618)(OB619), —OSi(B620)(B621)(B622),        —OS(O₂)—B623, —NHC(O)—NH₂, —NHC(O)—B624, —NB625C(O)—B626,        —NH—C(O)—O-8627, —NH—C(O)—NH—B628, —NH—C(O)—NB629B630,        —NB631-C(O)—O—B632, —NB633-C(O)—NH—B634, —NB635-C(O)—NB636B637,        —NHS(O₂)—B638, —NB639S(O₂)—B640, —S—B641, —S(O)—B642,        —S(O₂)—B643, —S(O₂)NH—B644, —S(O₂)NB645B646, —S(O₂)O—B647,        —P(O)(OB648)(OB649), —Si(B650)(B651)(B652), —C(NH)—NH₂,        —C(NB653)-NH₂, —C(NH)—NHB654, —C(NH)—NB655B656,        —C(NB657)-NHB658, —C(NB659)-NB660B661, —NH—C(O)—NH—O—B662,        —NH—C(O)—NB663-O—B664, —NB665-C(O)—NB666-O—B667,        —N(—C(O)—NH—O—B668)₂, —N(—C(O)—NB669-O—B670)₂,        —N(—C(O)—NH—O—B671)(—C(O)—NB672-O—B673), —C(S)—B674,        —C(S)—O—B675, —C(S)—NH—B676, —C(S)—NB677B678, —C(O)—NH—O—B679,        —C(O)—NB680-O—B681, —C(S)—NH—O—B682, —C(S)—NB683-O—B684,        —C(O)—NH—NH—B685, —C(O)—NH—NB686B687, —C(O)—NB688-NB689B690,        —C(S)—NH—NH—B691, —C(S)—NH—NB692B693, —C(S)—NB694-NB695B696,        —C(O)—C(O)—O—B697, —C(O)—C(O)—NH₂, —C(O)—C(O)—NHB698,        —C(O)—C(O)—NB699B700, —C(S)—C(O)—O—B701, —C(O)—C(S)—O—B702,        —C(S)—C(S)—O—B703, —C(S)—C(O)—NH₂, —C(S)—C(O)—NHB704,        —C(S)—C(O)—NB705B706, —C(S)—C(S)—NH₂, —C(S)—C(S)—NHB707,        —C(S)—C(S)—NB708B709, —C(O)—C(S)—NH₂, —C(O)—C(S)—NHB710,        —C(O)—C(S)—NB711B712”;        -   wherein B601, B602, B603, B604, B605, B606, B607, B608,            B609, B610, B611, B612, B613, B614, B615, B616, B617, B618,            B619, B620, B621, B622, B623, B624, B625, B626, B627, B628,            B629, B630, B631, B632, B633, B634, B635, B636, B637, B638,            B639, B640, B641, B642, B643, B644, B645, B646, B647, B648,            B649, B650, B651, B652, B653, B654, B655, B656, B657, B658,            B659, B660, B661, B662, B663, B664, B665, B666, B667, B668,            B669, B670, B671, B672, B673, B674, B675, B676, B677, B678,            B679, B680, B681, B682, B683, B684, B685, B686, B687, B688,            B689, B690, B691, B692, B693, B694, B695, B696, B697, B698,            B699, B700, B701, B702, B703, B704, B705, B706, B707, B708,            B709, B710, B711, B712 are independently from each other            selected from the group consisting of: “hydrogen, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl” and wherein alternatively B607, B608 and/or            B616, B617 and/or 8629, B630 and/or B636, B637 and/or B645,            B646 and/or 8655, B656 and/or B660, B661 and/or B677, B678            and/or B686, B687 and/or B689, B690 and/or B692, B693 and/or            B695, B696 and/or 8699, B700 and/or B705, B706 and/or B708,            B709 and/or B711, B712 and/or respectively together can also            form “heterocyclyl”.

In order to avoid ambiguities, the cases (1)(a) to (d) detailed abovefor the general formula (I) are to establish novelty over the prior artas follows: novelty is established by the fact that at least one ofradicals R3, R4 must be one of the substituents as illustrated under (1)(a), (b), (c) and (d), whereas the other one of radicals R3, R4 can beeither one of the substituents as illustrated under (1) (a), (b), (c)and (d) or it can be one of the substituents as illustrated under (2).Radicals R1, R2 and R5 can in all cases be one of the substituents asillustrated under (3).

In a preferred embodiment, pyrido[2,3-b]pyrazine derivatives accordingto above general formula (I) are provided, wherein:

radical R1 independently is selected from the group consisting of:

-   -   (i) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl, —NH-alkyl, —NH—(C₉-C₃₀)alkyl,        —NH-cycloalkyl, —NH-cycloalkylalkyl, —NH-aryl, —NH-arylalkyl,        —NH-heteroaryl, —NH-heteroarylalkyl, —NH-heterocyclyl,        —NH-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R2 independently is “hydrogen”;

radical R3 independently is selected from the group consisting of:

-   -   (i) “—NH—C(O)—NH—C(O)—O-alkyl, —NH—C(O)—NH—C(O)—O—(C₉-C₃₀)alkyl,        —NH—C(O)—NH—C(O)—O-cycloalkyl,        —NH—C(O)—NH—C(O)—O-cycloalkylalkyl, —NH—C(O)—NH—C(O)—O-aryl,        —NH—C(O)—NH—C(O)—O-arylalkyl, —NH—C(O)—NH—C(O)—O-heteroaryl,        —NH—C(O)—NH—C(O)—O-heteroarylalkyl,        —NH—C(O)—NH—C(O)—O-heterocyclyl,        —NH—C(O)—NH—C(O)—O-heterocyclylalkyl —NH—C(S)—NH-alkyl,        —NH—C(S)—NH—(C₉-C₃₀)alkyl, —NH—C(S)—NH-cycloalkyl,        —NH—C(S)—NH-cycloalkylalkyl, —NH—C(S)—NH-aryl,        —NH—C(S)—NH-arylalkyl, —NH—C(S)—NH-heteroaryl,        —NH—C(S)—NH-heteroarylalkyl, —NH—C(S)—NH-heterocyclyl,        —NH—C(S)—NH-heterocyclylalkyl, —NH—C(═NH)-alkyl,        —NH—C(═NH)—(C₉-C₃₀)alkyl, —NH—C(═NH)-cycloalkyl,        —NH—C(═NH)-cycloalkylalkyl, —NH—C(═NH)-aryl,        —NH—C(═NH)-arylalkyl, —NH—C(═NH)-heteroaryl,        —NH—C(═NH)-heteroarylalkyl, —NH—C(═NH)-heterocyclyl,        —NH—C(═NH)-heterocyclylalkyl, —NH—C(O)—C(O)-alkyl,        —NH—C(O)—C(O)—(C₉-C₃₀)alkyl, —NH—C(O)—C(O)-cycloalkyl,        —NH—C(O)—C(O)-cycloalkylalkyl, —NH—C(O)—C(O)-aryl,        —NH—C(O)—C(O)-arylalkyl, —NH—C(O)—C(O)-heteroaryl,        —NH—C(O)—C(O)-heteroarylalkyl, —NH—C(O)—C(O)-heterocyclyl,        —NH—C(O)—C(O)-heterocyclylalkyl”        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R4 independently is selected from the group consisting of:

-   -   (i) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl, —NH-alkyl, —NH—(C₉-C₃₀)alkyl,        —NH-cycloalkyl, —NH-cycloalkylalkyl, —NH-aryl, —NH-arylalkyl,        —NH-heteroaryl, —NH-heteroarylalkyl, —NH-heterocyclyl,        —NH-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R5 independently is “hydrogen”.

In a further preferred embodiment, pyrido[2,3-b]pyrazine derivativesaccording to above general formula (I) are provided, wherein:

radical R1 independently is selected from the group consisting of:

-   -   (i) “hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl,        hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl, —NH—R_(x1)” with R_(x), being selected        from the group consisting of: “methyl, ethyl, propyl, isopropyl,        tert-butyl, hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanyl—propyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R₂ independently is “hydrogen”;

radical R₃ independently is selected from the group consisting of:

-   -   (i) “—NH—C(O)—NH—C(O)—O—R_(x2), —NH—C(S)—NH—R_(x3),        —NH—C(═NH)—R_(x4), —NH—C(O)—C(O)—R_(x5)”, with R_(x2), R_(x3),        R_(x4), R_(x5) independently from each other being selected from        the group consisting of: “methyl, ethyl, propyl, isopropyl,        tert-butyl, hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;    -   where above substituents of substituents group (i)—if not        hydrogen or nitrogen—may, optionally, additionally be        substituted with at least one substituent selected from the        group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO,        —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —NHC(O)—NH₂, —C(NH)—NH₂,        —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, alkyl-OH, alkyl-CN,        alkyl-COOH, alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,        aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,        —C(O)—O-alkyl, —C(O)—O-heterocyclyl,        —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂, —OS(O₂)-alkyl,        —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl, —O-heterocyclyl,        —O-heterocyclylalkyl, —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,        —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl, —O-alkyl-F,        —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl, —OC(O)—N(alkyl)₂,        —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl, —OC(O)—O-alkyl,        —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl, —N(alkyl)₂, —N(aryl)₂,        —NHC(O)-alkyl, —NHC(O)-alkyl-NH-alkyl,        —NHC(O)-alkyl-C(O)—O-alkyl, —NHC(O)—O-alkyl,        —NHC(O)—O-alkyl-O-alkyl,        —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,        —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl, —NHC(O)—NH-heterocyclyl,        —NHC(O)—NH-heterocyclylalkyl, —NHC(O)—NH-alkyl-halogen,        —NHC(O)—NH-alkyl-C1, —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R4 independently is selected from the group consisting of:

-   -   (i) “hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl,        hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl, —NH—R_(x6)” with R_(x6) being selected        from the group consisting of: “methyl, ethyl, propyl, isopropyl,        tert-butyl, hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinyipropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;    -   where above substituents of substituents group (i)—if not        hydrogen or nitrogen—may, optionally, additionally be        substituted with at least one substituent selected from the        group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂,        —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO,        —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —NHC(O)—NH₂, —C(NH)—NH₂,        —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, alkyl-OH, alkyl-CN,        alkyl-COOH, alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,        aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,        —C(O)—O-alkyl, —C(O)—O-heterocyclyl,        —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂, —OS(O₂)-alkyl,        —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl, —O-heterocyclyl,        —O-heterocyclylalkyl, —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,        —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl, —O-alkyl-F,        —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl, —OC(O)—N(alkyl)₂,        —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl, —OC(O)—O-alkyl,        —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl, —N(alkyl)₂, —N(aryl)₂,        —NHC(O)-alkyl, —NHC(O)-alkyl-NH-alkyl,        —NHC(O)-alkyl-C(O)—O-alkyl, —NHC(O)—O-alkyl,        —NHC(O)—O-alkyl-O-alkyl,        —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, NHC(O)—NH-alkyl,        —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl, —NHC(O)—NH-heterocyclyl,        —NHC(O)—NH-heterocyclylalkyl, —NHC(O)—NH-alkyl-halogen,        —NHC(O)—NH-alkyl-Cl, —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R5 independently is “hydrogen”.

In a further preferred embodiment, pyrido[2,3-b]pyrazine derivativesaccording to above general formula (I) and preferred embodiments andsubsets are provided, wherein:

radical R1 independently is selected from the group consisting of:

-   -   (i) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl, —NH-alkyl, —NH—(C₉-C₃₀)alkyl,        —NH-cycloalkyl, —NH-cycloalkylalkyl, —NH-aryl, —NH-arylalkyl,        —NH-heteroaryl, —NH-heteroarylalkyl, —NH-heterocyclyl,        —NH-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R2 independently is “hydrogen”;

radical R3 independently is selected from the group consisting of:

-   -   (i) “—NH—C(O)—NH₂, —NH—C(O)—NH-alkyl, —NH—C(O)—NH—(C₉-C₃₀)alkyl,        —NH—C(O)—NH-cycloalkyl, —NH—C(O)—NH-cycloalkylalkyl,        —NH—C(O)—NH-aryl, NH—C(O)—NH-arylalkyl, —NH—C(O)—NH-heteroaryl,        —NH—C(O)—NH-heteroarylalkyl, —NH—C(O)—NH-heterocyclyl,        —NH—C(O)—NH-heterocyclylalkyl, —NH—C(O)—O-alkyl,        —NH—C(O)—O—(C₉-C₃₀)alkyl, —NH—C(O)—O-cycloalkyl,        —NH—C(O)—O-cycloalkylalkyl, —NH—C(O)—O-aryl,        —NH—C(O)—O-arylalkyl, —NH—C(O)—O-heteroaryl,        —NH—C(O)—O-heteroarylalkyl, —NH—C(O)—O-heterocyclyl,        —NH—C(O)—O-heterocyclylalkyl, —NH—C(O)-alkyl,        —NH—C(O)—(C₉-C₃₀)alkyl, —NH—C(O)-cycloalkyl,        —NH—C(O)-cycloalkylalkyl, —NH—C(O)-aryl, —NH—C(O)-arylalkyl,        —NH—C(O)-heteroaryl, —NH—C(O)-heteroarylalkyl,        —NH—C(O)-heterocyclyl, —NH—C(O)-heterocyclylalkyl,        —NH—S(O₂)-alkyl, —NH—S(O₂)—(C₉-C₃₀)alkyl, —NH—S(O₂)-cycloalkyl,        —NH—S(O₂)-cycloalkylalkyl, —NH—S(O₂)-aryl, —NH—S(O₂)-arylalkyl,        —NH—S(O₂)-heteroaryl, —NH—S(O₂)-heteroarylalkyl,        —NH—S(O₂)-heterocyclyl, —NH—S(O₂)-heterocyclylalkyl;        -   where above substituents of substituents group (i)—if not            hydrogen, nitrogen or sulphur—may, optionally, additionally            be substituted with at least one substituent selected from            the group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R4 independently is selected from the group consisting of:

-   -   (i) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl, —NH-alkyl, —NH—(C₉-C₃₀)alkyl,        —NH-cycloalkyl, —NH-cycloalkylalkyl, —NH-aryl, —NH-arylalkyl,        —NH-heteroaryl, —NH-heteroarylalkyl, —NH-heterocyclyl,        —NH-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R5 independently is selected from the group consisting of:

-   -   (i) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen—may, optionally, additionally be substituted with            at least one substituent selected from the group consisting            of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃, —NH₂, —NO₂, —OH, ═O,            —OCF₃, —OCHF₂, —SH, —O—SO₃H, —OP(O)(OH)₂, —CHO, —COON,            —C(O)NH₂, —SO₃H, —P(O)(OH)₂, —NHC(O)—NH₂, —C(NH)—NH₂,            —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,            cycloalkylalkyl, heterocyclyl, heterocyclylalkyl, aryl,            arylalkyl, heteroaryl, heteroarylalkyl, alkyl-OH, alkyl-CN,            alkyl-COON, alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”.

In a yet further preferred embodiment, pyrido[2,3-b]pyrazine derivativesaccording to above general formula (I) and preferred embodiments andsubsets are provided, wherein:

radical R1 independently is selected from the group consisting of:

-   -   (i) “hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl,        hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropyl-propyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-3-yl, pyridin-4-yl, pyrazolyl, pyrazol-3-yl,        pyrazol-4-yl, quinolinyl, quinolin-2-yl, quinolin-3-yl,        quinolin-4-yl, quinolin-8-yl, thiophenyl, thiophen-2-yl,        thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl, pyrimidinyl,        pyrimidin-5-yl, imidazolyl, imidazol-4-yl, imidazol-3-yl,        pyrrolo[2,3-b]pyridinyl, pyrrolo[2,3-b]pyridin-5-yl, indolyl,        1H-indol-2-yl, dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinyl-methyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl, —NH—R_(y),” with R_(y), being selected        from the group consisting of: “methyl, ethyl, propyl, isopropyl,        tert-butyl, hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentyl-propyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R2 independently is “hydrogen”;

radical R3 independently is selected from the group consisting of:

-   -   (i) “—NH—C(O)—NH₂, —NH—C(O)—NH—R_(y2), —NH—C(O)—O—R_(y3),        —NH—C(O)—R_(y4), —NH—S(O₂)—R_(y5)”;        -   with R_(y2), R_(y3), R_(y4), R_(y5) independently from each            other being selected from the group consisting of: “methyl,            ethyl, propyl, isopropyl, tert-butyl, hexyl, allyl,            propenyl, prop-2-en-1-yl, cyclopropyl, cyclopropylmethyl,            cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl,            cyclopentyl, cyclopentylmethyl, cyclopentylethyl,            cyclopentylpropyl, cyclopentylbutyl, cyclohexyl,            cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,            cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,            naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,            pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,            pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,            quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,            thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl,            furan-3-yl, pyrimidinyl, pyrimidin-5-yl, imidazolyl,            imidazol-4-yl, imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,            pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,            dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,            piperidinylmethyl, piperidinylethyl, piperidinyipropyl,            piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,            piperidin-4-yl, piperazinyl, piperazinylmethyl,            piperazinylethyl, piperazinylpropyl, piperazinylbutyl,            piperazin-1-yl, diazepanyl, diazepanylmethyl,            diazepanylethyl, diazepanylpropyl, diazepanylbuytl,            diazepan-1-yl, morpholinyl, morpholinylmethyl,            morpholinylethyl, morpholinylpropyl, morpholinylbuytyl,            morpholin-4-yl, 2-morpholin-4-yl-ethyl,            1,2,3,4-tetrahydro-isoquinolinyl,            1,2,3,4-tetrahydro-isoquinolinylmethyl,            1,2,3,4-tetrahydro-isoquinolinylethyl,            1,2,3,4-tetrahydro-isoquinolinylpropyl,            1,2,3,4-tetrahydro-isoquinolinylbutyl,            1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,            benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,            benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,            benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,            benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,            benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,            benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen, nitrogen or sulphur—may, optionally, additionally            be substituted with at least one substituent selected from            the group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R4 independently is selected from the group consisting of:

-   -   (i) “hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl,        hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropyl-propyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinyl-methyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl, —NH—R_(A)” with R_(A) being selected from        the group consisting of: “methyl, ethyl, propyl, isopropyl,        tert-butyl, hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentyl-propyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl,        cyclo-hexylpropyl, cyclohexylbutyl, phenyl, naphthalenyl,        naphthalen-1-yl, naphthalen-2-yl, benzyl, phenyl-ethyl,        isoxazol, pyridinyl, pyridin-2-yl, pyridin-3-yl, pyridin-4-yl,        pyrazolyl, pyrazol-3-yl, pyrazol-4-yl, quinolinyl,        quinolin-2-yl, quinolin-3-yl, quinolin-4-yl, quinolin-8-yl,        thiophenyl, thiophen-2-yl, thiophen-3-yl, furanyl, fu-ran-2-yl,        furan-3-yl, pyrimidinyl, pyrimidin-5-yl, imidazolyl,        imidazol-4-yl, imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanyl-propyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R5 independently is selected from the group consisting of:

-   -   (i) “hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl,        hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropyl-propyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanyipropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinyl-methyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

In another preferred embodiment, pyrido[2,3-b]pyrazine derivativesaccording to above general formula (I) and preferred embodiments andsubsets are provided, wherein:

radical R1 independently is selected from the group consisting of:

-   -   (i) “—NH—C(O)—NH₂, —NH—C(S)—NH₂, —NH—C(O)—NH-alkyl,        —NH—C(O)—NH—(C₉-C₃₀)alkyl, —NH—C(O)—NH-cycloalkyl,        —NH—C(O)—NH-cycloalkylalkyl, —NH—C(O)—NH-aryl,        —NH—C(O)—NH-arylalkyl, —NH—C(O)—NH-heteroaryl,        —NH—C(O)—NH-heteroarylalkyl, —NH—C(O)—NH-heterocyclyl,        —NH—C(O)—NH-heterocyclylalkyl, —NH—C(S)—NH-alkyl,        —NH—C(S)—NH—(C₉-C₃₀)alkyl, —NH—C(S)—NH-cycloalkyl,        —NH—C(S)—NH-cycloalkylalkyl, —NH—C(S)—NH-aryl,        —NH—C(S)—NH-arylalkyl, —NH—C(S)—NH-heteroaryl,        —NH—C(S)—NH-heteroarylalkyl, —NH—C(S)—NH-heterocyclyl,        —NH—C(S)—NH-heterocyclylalkyl, —NH—C(O)-alkyl,        —NH—C(O)—(C₉-C₃₀)alkyl, —NH—C(O)-cycloalkyl,        —NH—C(O)-cycloalkylalkyl, —NH—C(O)-aryl, —NH—C(O)-arylalkyl,        —NH—C(O)-heteroaryl, —NH—C(O)-heteroarylalkyl,        —NH—C(O)-heterocyclyl, —NH—C(O)—heterocyclylalkyl,        —NH—C(S)-alkyl, —NH—C(S)—(C₉-C₃₀)alkyl, —NH—C(S)-cycloalkyl,        —NH—C(S)-cycloalkylalkyl, —NH—C(S)-aryl, —NH—C(S)-arylalkyl,        —NH—C(S)-heteroaryl, —NH—C(S)-heteroarylalkyl,        —NH—C(S)-heterocyclyl, —NH—C(S)-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen, nitrogen or sulphur—may, optionally, additionally            be substituted with at least one substituent selected from            the group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-1, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R2 independently is “hydrogen”;

radical R3 independently is selected from the group consisting of:

-   -   (i) “alkyl, (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, aryl,        arylalkyl, heteroaryl, heteroarylalkyl, heterocyclyl,        heterocyclylalkyl, —NH-alkyl, —NH—(C₉-C₃₀)alkyl, —NH-cycloalkyl,        —NH-cycloalkylalkyl, —NH-aryl, —NH-arylalkyl, —NH-heteroaryl,        —NH-heteroarylalkyl, —NH-heterocyclyl, —NH-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R4 independently is selected from the group consisting of:

-   -   (i) “hydrogen, alkyl, (C₉-C₃₀)alkyl, cycloalkyl,        cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,        heterocyclyl, heterocyclylalkyl, —NH-alkyl, —NH—(C₉-C₃₀)alkyl,        —NH-cycloalkyl, —NH-cycloalkylalkyl, —NH-aryl, —NH-arylalkyl,        —NH-heteroaryl, —NH-heteroarylalkyl, —NH-heterocyclyl,        —NH-heterocyclylalkyl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R5 independently is “hydrogen”.

In yet another preferred embodiment, pyrido[2,3-b]pyrazine derivativesaccording to above general formula (I) and preferred embodiments andsubsets are provided, wherein:

radical R₁ independently is selected from the group consisting of:

-   -   (i) “—NH—C(O)—NH₂, —NH—C(S)—NH₂, —NH—C(O)—NH—R₁₁,        —NH—C(S)—NH—R_(z2), —NH—C(O)—R_(y3), —NH—C(S)—NH—R_(z4)”, with        R_(z1), R_(z2), R_(z3), R_(z4) independently from each other        being selected from the group consisting of: “methyl, ethyl,        propyl, isopropyl, tert-butyl, hexyl, allyl, propenyl,        prop-2-en-1-yl, cyclopropyl, cyclopropylmethyl,        cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl,        cyclopentyl, cyclopentylmethyl, cyclopentylethyl,        cyclopentylpropyl, cyclopentylbutyl, cyclohexyl,        cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen, nitrogen or sulphur—may, optionally, additionally            be substituted with at least one substituent selected from            the group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COON, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-C1,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-I, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R2 independently is “hydrogen”;

radical R3 independently is selected from the group consisting of:

-   -   (i) “methyl, ethyl, propyl, isopropyl, tert-butyl, hexyl, allyl,        propenyl, prop-2-en-1-yl, cyclopropyl, cyclopropylmethyl,        cyclopropylethyl, cyclopropylpropyl, cyclopropylbutyl,        cyclopentyl, cyclopentylmethyl, cyclopentylethyl,        cyclopentylpropyl, cyclopentylbutyl, cyclohexyl,        cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl, —NH—R_(z5)” with R_(z5) being selected        from the group consisting of: “methyl, ethyl, propyl, isopropyl,        tert-butyl, hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropylpropyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinylmethyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COOH,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-1, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-C1,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R4 independently is selected from the group consisting of:

-   -   (i) “hydrogen, methyl, ethyl, propyl, isopropyl, tert-butyl,        hexyl, allyl, propenyl, prop-2-en-1-yl, cyclopropyl,        cyclopropylmethyl, cyclopropylethyl, cyclopropyl-propyl,        cyclopropylbutyl, cyclopentyl, cyclopentylmethyl,        cyclopentylethyl, cyclopentylpropyl, cyclopentylbutyl,        cyclohexyl, cyclohexylmethyl, cyclohexylethyl, cyclohexylpropyl,        cyclohexylbutyl, phenyl, naphthalenyl, naphthalen-1-yl,        naphthalen-2-yl, benzyl, phenyl-ethyl, isoxazol, pyridinyl,        pyridin-2-yl, pyridin-3-yl, pyridin-4-yl, pyrazolyl,        pyrazol-3-yl, pyrazol-4-yl, quinolinyl, quinolin-2-yl,        quinolin-3-yl, quinolin-4-yl, quinolin-8-yl, thiophenyl,        thiophen-2-yl, thiophen-3-yl, furanyl, furan-2-yl, furan-3-yl,        pyrimidinyl, pyrimidin-5-yl, imidazolyl, imidazol-4-yl,        imidazol-3-yl, pyrrolo[2,3-b]pyridinyl,        pyrrolo[2,3-b]pyridin-5-yl, indolyl, 1H-indol-2-yl,        dibenzofuranyl, dibenzofuran-4-yl, piperidinyl,        piperidinylmethyl, piperidinylethyl, piperidinylpropyl,        piperidinylbutyl, piperidin-1-yl, piperidin-3-yl,        piperidin-4-yl, piperazinyl, piperazinylmethyl,        piperazinylethyl, piperazinylpropyl, piperazinylbutyl,        piperazin-1-yl, diazepanyl, diazepanylmethyl, diazepanylethyl,        diazepanylpropyl, diazepanylbuytl, diazepan-1-yl, morpholinyl,        morpholinyl-methyl, morpholinylethyl, morpholinylpropyl,        morpholinylbuytyl, morpholin-4-yl, 2-morpholin-4-yl-ethyl,        1,2,3,4-tetrahydro-isoquinolinyl,        1,2,3,4-tetrahydro-isoquinolinylmethyl,        1,2,3,4-tetrahydro-isoquinolinylethyl,        1,2,3,4-tetrahydro-isoquinolinylpropyl,        1,2,3,4-tetrahydro-isoquinolinylbutyl,        1,2,3,4-tetrahydro-isoquinolin-7-yl, benzo[1,3]dioxolyl,        benzo[1,3]dioxolylmethyl, benzo[1,3]dioxolylethyl,        benzo[1,3]dioxolylpropyl, benzo[1,3]dioxolylbutyl,        benzo[1,3]dioxol-5-yl, benzo[1,4]oxazinyl,        benzo[1,4]oxazinylmethyl, benzo[1,4]oxazinylethyl,        benzo[1,4]oxazinylpropyl, benzo[1,4]oxazinylbutyl,        benzo[1,4]oxazin-6-yl”;        -   where above substituents of substituents group (i)—if not            hydrogen or nitrogen—may, optionally, additionally be            substituted with at least one substituent selected from the            group consisting of: “—F, —Cl, —Br, —I, —CN, —CF₃, —N₃,            —NH₂, —NO₂, —OH, ═O, —OCF₃, —OCHF₂, —SH, —O—SO₃H,            —OP(O)(OH)₂, —CHO, —COOH, —C(O)NH₂, —SO₃H, —P(O)(OH)₂,            —NHC(O)—NH₂, —C(NH)—NH₂, —C(O)—C(O)—NH₂, —C(O)—CF₃, alkyl,            (C₉-C₃₀)alkyl, cycloalkyl, cycloalkylalkyl, heterocyclyl,            heterocyclylalkyl, aryl, arylalkyl, heteroaryl,            heteroarylalkyl, alkyl-OH, alkyl-CN, alkyl-COON,            alkyl-P(O)(O-alkyl)₂, cycloalkyl-CN, aryl-OH,            aryl(—OH)(-alkyl), —C(O)-alkyl, —C(O)-heterocyclyl,            —C(O)—O-alkyl, —C(O)—O-heterocyclyl,            —P(O)(O-alkyl-O—C(O)-alkyl)₂, —OP(O)(O-alkyl)₂,            —OS(O₂)-alkyl, —S-alkyl, —O-alkyl, —O-aryl, —O-arylalkyl,            —O-heterocyclyl, —O-heterocyclylalkyl,            —O-arylalkyl-(O-alkyl)₂, —O-alkyl-O-alkyl,            —O-alkyl-N(alkyl)₂, —O-alkyl-halogen, —O-alkyl-Cl,            —O-alkyl-F, —O-alkyl-Br, —O-alkyl-1, —OC(O)-alkyl,            —OC(O)—N(alkyl)₂, —OC(O)—NH-alkyl, —OC(O)—(C₉-C₃₀)alkyl,            —OC(O)—O-alkyl, —OC(O)—O-alkyl-O-alkyl, —OC(O)—O-aryl,            —N(alkyl)₂, —N(aryl)₂, —NHC(O)-alkyl,            —NHC(O)-alkyl-NH-alkyl, —NHC(O)-alkyl-C(O)—O-alkyl,            —NHC(O)—O-alkyl, —NHC(O)—O-alkyl-O-alkyl,            —NHC(O)—O-alkyl-O-alkyl-O-alkyl-O-alkyl, —NHC(O)—NH-alkyl,            —NHC(O)—NH-aryl, —NHC(O)—NH-heteroaryl,            —NHC(O)—NH-heterocyclyl, —NHC(O)—NH-heterocyclylalkyl,            —NHC(O)—NH-alkyl-halogen, —NHC(O)—NH-alkyl-Cl,            —NHC(O)—N(alkyl)₂, —NHS(O₂)-alkyl”;

radical R5 independently is “hydrogen”.

In another preferred embodiment, pyrido[2,3-b]pyrazine derivativesaccording to general formula (I) and above preferred embodiments andsubsets are provided that are selected from the group consisting of:

Com- pound Structure Name  1

1-Ethyl-3-(6-p- tolylamino-pyrido[2,3- b]pyrazin-3-yl)-urea  2

1-[6-(4-Amino-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea  3

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenyl-urea  4

1-Ethyl-3-(6-phenyl- pyrido[2,3-b]pyrazin- 3-yl)-urea  5

1-Ethyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea  6

1-[6-(4-Chloro- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3- ethyl-urea  7

1-Ethyl-3-(6-pyridin- 4-yl-pyrido[2,3- b]pyrazin-3-yl)-urea  8

1-[6-(3-Chloro-4- hydroxy-5-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3- ethyl-urea  9

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea  10

1-Ethyl-3-[6-(1- methyl-1H-pyrazol-4- yl)-pyrido[2,3-b]pyrazin-3-yl]-urea  11

1-Ethyl-3-[6-(4- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea  12

1-Ethyl-3-[6-(3- isopropoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-urea  13

1-Ethyl-3-(6- phenylamino- pyrido[2,3-b]pyrazin- 3-yl)-urea  14

1-Phenyl-3-(6- phenylamino- pyrido[2,3-b]pyrazin- 3-yl)-urea  15

1-[6-(3,5-Dichloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea  16

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-propyl-urea  17

1-Cyclohexyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea  18

1-Allyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea  19

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-isopropyl-urea  20

1-Cyclopentyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea  21

1-Ethyl-3-[6-(4- hydroxy-3-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-urea  22

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3- ethyl-urea 23

1-Ethyl-3-[6-(3,4,5- trimethoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-urea  24

1-Ethyl-3-[6-(4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea 25

1-Ethyl-3-(6-p- tolylamino-pyrido[2,3- b]pyrazin-3-yl)- thiourea  26

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenethyl- urea  27

1-(3,5-Dimethyl- isoxazol-4-yl)-3-[6-(4- hydroxy-3-methoxy-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-urea  28

1-tert-Butyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea  29

1-Benzyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea  30

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-1-[1-(2,2,2- trifluoro-acetyl)- piperidin-4-yl]-urea  31

1-[6-(3-Chloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea  32

1-Ethyl-3-[6-(quinolin- 3-ylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea  33

2,2-Dimethyl- propionic acid(2,2- dimethyl- propionyloxymeth-oxy)-[4-(3-{3-[4-(2,2- dimethyl-propionyl- oxy)-3-methoxy-phenyl]-pyrido[2,3- b]pyrazin-6-yl}- ureido)-butyl]- phosphinoyloxy-methyl ester  34

Phosphoric acid di- ethyl ester 4-[6-(3- ethyl-ureido)-pyrido[2,3-b]-pyrazin- 3-yl]-2-methoxy- phenyl ester  35

1-Ethyl-3-[3-(4- methyl-3,4-dihydro- 2H-benzo[1,4]oxazin-6-yl)-pyrido[2, 3-b]pyrazin-6-yl]-urea  36

N-[3-(3-Isopropoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-acetamide 37

Methanesulfonic acid 2-chloro-4-[6-(3-ethyl- ureido)-pyrido[2,3-b]pyrazin-3-yl]-6- methoxy-phenyl ester  38

[3-(3-Isopropoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-carbamicacid ethyl ester  39

1-{3-[4-(2-Chloro- ethoxy)-3-methoxy- phenyl]-pyrido[2,3-b]pyrazin-6-yl}- 3-ethyl-urea  40

{4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-yl]-2-methoxy-phenyl}-carbamic acid 2-methoxy-ethyl ester  41

Phosphoric acid mono-{4-[6-(3-ethyl- ureido)-pyrido-[2,3-b]pyrazin-3-yl]-2- methoxy-phenyl} es- ter; sodium salt  42

1-[3-(2,2-Difluoro- benzo[1,3]dioxol-5- ylamino)-pyrido[2,3-b]pyrazin-6-yl]-3- ethyl-urea  43

Methanesulfonic acid 4-[6-(3-ethyl-ureido)- pyrido[2,3-b]pyrazin-3-yl]-2-methoxy- phenyl ester  44

{4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-yl]-2-methoxy-phenyl}-carbamic acid 2-[2-(2-methoxy- ethoxy)-ethoxy]-ethyl ester  45

{3-[6-(3-Ethyl-ureido)- pyrido[2,3-b]-pyrazin- 3-ylamino]-phenyl}-acetic acid  46

1-Ethyl-3-[3-(3- hydroxy-4-methoxy- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea  47

1-[3-(3-Bromo-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  48

1-Ethyl-3-{3-[4- (morpholine-4- carbonyl)- phenylamino]-pyrido[]2,3-b]}-pyrazin- 6-yl}-urea  49

1-Cyclopropyl-3-[3- (3-isopropoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea  50

5-[6-(3-Ethyl-ureido)- pyrido[2,3-b]-pyrazin- 3-ylamino]-2-hydroxy-benzoic acid methyl ester  51

1-Ethyl-3-[3-(2- isopropoxy-pyridin-3- yl)-pyrido[2,3-b]pyrazin-6-yl]-urea  52

1-Ethyl-3-[3-(2H- pyrazol-3-yl)- pyrido[2,3-b]pyrazin- 6-yl]-urea  53

1-Ethyl-3-[3-(3- methyl-3H-imidazol- 4-yl)-pyrido[2,3-b]pyrazin-6-yl]-urea  54

Acetic acid 4-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin-3-yl]-2-methoxy- phenyl ester  55

1-Ethyl-3-[3-(2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea 56

1-Ethyl-3-[3-(3- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea 57

1-[3-(2-Benzyloxy- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea  58

1-[3-(1-Benzyl-1H- pyrazol-4-yl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  59

1-Ethyl-3-[3-(1- isobutyl-1H-pyrazol- 4-yl)-pyrido[2,3-b]pyrazin-6-yl]-urea  60

1-Ethyl-3-{3-[1-(2- morpholin-4-yl-ethyl)- 1H-pyrazol-4-yl]-pyrido[2,3-b]pyrazin- 6-yl}-urea  61

1-Ethyl-3-[3-(1H- pyrrolo[2,3-b]pyridin- 5-yl)-pyrido[2,3-b]pyrazin-6-yl]-urea  62

1-Ethyl-3-[3-(2- isobutoxy-phenyl)- pyrido[2,3-b]pyrazin- 6-yl]-urea  63

1-Ethyl-3-{3-[3- methoxy-4-(3- morpholin-4-yl- propoxy)-phenyl]-pyrido[2,3-b]pyrazin- 6-yl}-urea  64

1-Ethyl-3-(3- phenylamino-pyrido- [2,3-b]pyrazin-6-yl)- urea  65

1-[3-(3-Isopropoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-(4-morpholin- 4-yl-butyl)-urea  66

2-Acetylamino-N-(3- p-tolylamino-pyr ido[2,3-b]pyrazin-6- yl)-acetamide 67

1-[3-(3-Bromo-2- isoporopoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  68

1-[3-(2,3-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 70

1-Ethyl-3-[3-(1H- indol-2-yl)-pyrido[2,3- b]pyrazin-6-yl]-urea  71

1-(3-Dibenzofuran-4- yl-pyrido[2,3- b]pyrazin-6-yl)-3- ethyl-urea  72

1-[3-(2-Amino- pyrimidin-5-yl)- pyrido[2,3-b]pyrazin- 6-yl]-3-ethyl-urea 73

1-[3-(3- Difluoromethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  74

1-{3-[4-(1,1-Dioxo- 1lambda*6*- thiomorpholin-4- ylmethyl)-phenylamino]- pyrido[2,3-b]pyrazin- 6-yl}-3-ethyl-urea  75

1-Ethyl-3-[3-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-thiourea  76

N-{4-[6-(3-Ethyl- ureido)-pyrido[2,3- b]pyrazin-3-yl]-phenyl}-succinamic acid methyl ester  77

N-{4-[6-(3-Ethyl- ureido)-pyrido[2,3- b]pyrazin-3-yl]-2-methoxy-phenyl}- acetamide  78

1-[3-(4-Amino-3-nitro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 79

1-[3-(5-Acetyl-2- fluoro-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  80

1-Ethyl-3-[3-(4- methoxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-urea  81

1-Ethyl-3-[3-(3,4,5- trifluoro-phenyl)- pyrido[2,3-b]pyrazin- 6-yl]-urea 82

1-[3-(3,5-Dimethyl- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 83

1-Ethyl-3-[3-(3-fluoro- 4-methyl-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-urea  84

1-Ethyl-3-[3-(3-fluoro- biphenyl-4-yl)- pyrido[2,3-b]pyrazin- 6-yl]-urea 85

1-Ethyl-3-[3-(4- methyl-3-nitro- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea  86

1-Ethyl-3-[3-(4- hydroxy-3-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea  87

4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-2-methoxy-benzoic acid methyl ester  88

1,1′-(3,3′-(4-(2- (dimethyl- amino)ethoxy)phenyl azanediyl)bis(pyrido[2,3-b]pyrazin-6,3- diyl))bis(3-ethylurea)  89

1-Ethyl-3-[3-(3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea 90

1-[3-(3,5-Dichloro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 91

1-[3-(5-Chloro-2- methoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  92

1-[3-(2,5-Dichloro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 93

1-Ethyl-3-[3-(5-fluoro- 2-methoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-urea  94

1-[3-(3-Bromo-5- methyl-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea  95

1-[3-(3,4-Difluoro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 96

1-[3-(5-Chloro-2- fluoro-3-methyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-3- ethyl-urea  97

1-Ethyl-3-[3-(2- trifluoromethyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea  98

1-Ethyl-3-[3-(4- methoxy-2-methyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea  99

1-[3-(3-Chloro-2- fluoro-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 100

1-Ethyl-3-(3-m-tolyl- pyrido[2,3-b]pyrazin- 6-yl)-urea 101

1-Ethyl-3-[3-(3-nitro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-urea 102

1-[3-(2-Ethoxy- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 103

1-Ethyl-3-[3-(2-fluoro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-urea 104

1-[3-(2-Chloro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 105

1-Ethyl-3-(3-o-tolyl- pyrido[2,3-b]pyrazin- 6-yl)-urea 106

1-Ethyl-3-[3-(5-fluoro- 2-methyl-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-urea 107

1-[3-(2,3-Dimethyl- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea108

1-[3-(2,3-Dichloro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea109

1-[3-(2-Benzyloxy-3- bromo-5-methyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-3- ethyl-urea 110

1-[3-(3-Bromo-2- methoxy-5-methyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-3- ethyl-urea 111

1-[3-(3-Chloro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 112

1-[3-(2-Ethoxy-4- fluoro-phenyl)-pyr ido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 113

1-Ethyl-3-[3-(1- methyl-1H-pyrazol-4- yl)-pyrido[2,3- b]pyrazin-6-yl]-thiourea 114

1-[3-(3-Cyano- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 115

1-Ethyl-3-[3-(3- hydroxymethyl- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-urea116

1-(3-Biphenyl-3-yl- pyrido[2,3-b]pyrazin- 6-yl)-3-ethyl-urea 117

1-Ethyl-3-[3-(3- methylsulfanyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea 118

1-Ethyl-3-[3-(3- trifluoromethoxy- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea 119

3-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-yl]-benzoic acid ethylester 120

N-{3-[6-(3-Ethyl- ureido)-pyrido[2,3- b]pyrazin-3-yl]- phenyl}-methanesulfonamide 121

1-{3-[3-(3,5- Dimethoxy- benzyloxy)-phenyl]- pyrido[2,3-b]pyrazin-6-yl}-3-ethyl-urea 122

1-[3-(4-Chloro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 123

1-(3-Biphenyl-4-yl- pyrido[2,3-b]pyrazin- 6-yl)-3-ethyl-urea 124

1-Ethyl-3-(3-p-tolyl- pyrido[2,3-b]pyrazin- 6-yl)-thiourea 125

1-Ethyl-3-[3-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]- thiourea 126

1-Ethyl-3-(3-p- tolylamino-pyrido[2,3- b]pyrazin-6-yl)- thiourea 127

1-Ethyl-3-[3-(3- isopropoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 128

1-[3-(4- Diphenylamino- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3-ethyl-urea 129

1-Ethyl-3-[3-(3-fluoro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-urea 130

1-[3-(3-Ethoxy- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 131

1-Ethyl-3-[3-(4-nitro- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-urea 132

4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-yl]-benzoic acid methylester 133

1-Ethyl-3-[3-(4- propoxy-phenyl)- pyrido[2,3-b]pyrazin- 6-yl]-urea 134

1-Ethyl-3-[3-(3,4,5- trimethoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 135

1-Ethyl-3-[3-(2- methylsulfanyl- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-urea 136

1-[3-(3-Cyano- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 137

1-[3-(2-Chloro-6- methoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 138

1-[3-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 139

1-[3-(3-Chloro-4- hydroxy-5-methoxy- phenyl)-pyrido[2,3-b]pyrazin-6-yl]-3- ethyl-thiourea 140

1-[3-(4-Amino-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 141

1-Ethyl-3-(3- thiophen-3-yl- pyrido[2,3-b]pyrazin- 6-yl)-urea 142

1-[3-(3,4-Dimethyl- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea143

4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-yl]-2-fluoro-benzoic acidmethyl ester 144

1-[3-(3- Dimethylamino- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3-ethyl-urea 145

1-[3-(2,5-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea146

1-[3-(3-Ethoxy-2- fluoro-phenyl)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 147

1-Ethyl-3-[3-(3- hydroxy-4-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 148

1-Ethyl-3-(3- phenylamino- pyrido[2,3-b]pyrazin- 6-yl)-thiourea 149

1-Ethyl-3-[3-(2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 150

1-Ethyl-3-[3-(4- hydroxy-3-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 151

1-Ethyl-3-[3-(3,4,5- trimethyl-phenyl)- pyrido[2,3-b]pyrazin- 6-yl]-urea152

1-Ethyl-3-(3- thiophen-2-yl- pyrido[2,3-b]pyrazin- 6-yl)-urea 153

1-Ethyl-3-[3-(2- methoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea154

1-Ethyl-3-[3-(3- hydroxymethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 155

1-Ethyl-3-[3-(3- phenoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea156

1-Ethyl-3-[3-(3- hydroxy-4-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 157

1-[3-(3,5-Dimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-ethyl-thiourea 158

1-[3-(3-Chloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 159

1-[3-(3-Chloro-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 160

1-Ethyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 161

1-Ethyl-3-[3-(4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 162

1-Ethyl-3-[3-(3- methoxy-4-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 163

1-Ethyl-3-[3-(3- isopropoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 164

1-Ethyl-3-[3-(4- [1,2,4]triazol-1-yl- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 165

N-{5-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-2-methyl- phenyl}- methanesulfonamide 166

1-[3-(3,5-Dichloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 167

1-[3-(3-Chloro- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-ethyl-urea168

1-Ethyl-3-[3- (naphthalen-2- ylamino)-pyrido[2,3- b]pyrazin-6-yl]-thiourea 169

1-[3-(4- Dimethylamino- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 170

1-[3-(3-Acetyl- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-ethyl-urea171

[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea 172

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-methyl-urea 173

1-(2-Chloro-ethyl)-3- [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 174

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(2-morpholin- 4-yl-ethyl)-urea 175

176

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-pyridin-4-yl- urea 177

1-Ethyl-3-[6-(3- isopropoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea178

1-Ethyl-3-(6-p-tolyl- pyrido[2,3-b]pyrazin- 3-yl)-urea 179

1-[6-(3-Amino- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3- ethyl-urea 180

1-[6-(3-Amino-4- methyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 181

1-Ethyl-3-[6-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 182

1-Ethyl-3-[6-(4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea 183

1-[6-(5-Acetyl- thiophen-2-yl)- pyrido[2,3-b]pyrazin- 3-yl]-3-ethyl-urea184

1-[6-(5-Acetyl- thiophen-2-yl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 185

1-Ethyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 186

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 187

1-[6-(3-Chloro-4- hydroxy-5-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3- ethyl-thiourea 188

1-Ethyl-3-[6-(3- isopropoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 189

1-Ethyl-3-(6-p-tolyl- pyrido[2,3-b]pyrazin- 3-yl)-thiourea 190

1-Ethyl-3-[6-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 191

1-Ethyl-3-[6-(3,4,5- trimethoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 192

1-[6-(4-Amino-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 193

1-Ethyl-3-[6-(1- methyl-1H-pyrazol-4- yl)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 194

{3-[3-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 6-ylamino]-phenyl}- aceticacid 195

{3-[3-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 6-ylamino]-phenyl}-acetic acid 196

1-Ethyl-3-[6-(2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea197

1-Ethyl-3-[6-(2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 198

1-Ethyl-3-[6-(4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 199

1-Ethyl-3-[6-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-urea 200

1-Ethyl-3-[6-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 201

1-[6-(3-Chloro-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 202

1-[6-(3-Chloro-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 203

1-Ethyl-3-[6-(4- hydroxy-3-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 204

1-Ethyl-3-[6-(3- hydroxy-4-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-urea 205

1-Ethyl-3-[6-(3- hydroxy-4-methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 206

N-{5-[3-(3-Ethyl- ureido)-pyrido[2,3- b]pyrazin-6-ylamino]-2-methyl-phenyl}- methanesulfonamide 207

N-{5-[3-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin-6-ylamino]-2-methyl- phenyl}- methanesulfonamide 208

1-[6-(3-Chloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 209

1-Ethyl-3-[6-(3- methoxy-4-methyl- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-urea 210

1-Ethyl-3-[6-(3- methoxy-4-methyl- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 211

1-[6-(3-Amino-5- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 212

1-[6-(3-Amino-5- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 213

1-Ethyl-3-[6-(quinolin- 3-ylamino)- pyrido[2,3-b]pyrazin- 3-yl]-thiourea214

1-Ethyl-3-[6- (naphthalen-2- ylamino)-pyrido[2,3- b]pyrazin-3-yl]-urea215

1-Ethyl-3-[6- (naphthalen-2- ylamino)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 216

1-[6-(4-Chloro- phenylamino)- pyrido[2,3-b]pyrazin- 3-yl]-3-ethyl-urea217

1-[6-(4-Chloro- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 218

1-Ethyl-3-[6-(4- piperidin-1-ylmethyl- phenylamino)-pyrido[2,3-b]pyrazin- 3-yl]-urea 219

1-Ethyl-3-[6-(4- piperidin-1-ylmethyl- phenylamino)-pyrido[2,3-b]pyrazin- 3-yl]-thiourea 220

1-Ethyl-3-[6-(3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea221

1-Ethyl-3-[6-(3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 222

1-[6-(3- Difluoromethoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 223

1-[6-(3- Difluoromethoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 224

1-Ethyl-3-(6- phenylamino- pyrido[2,3-b]pyrazin- 3-yl)-thiourea 225

1-Ethyl-3-(6- morpholin-4-yl- pyrido[2,3-b]pyrazin- 3-yl)-urea 226

1-Ethyl-3-(6- morpholin-4-yl- pyrido[2,3-b]pyrazin- 3-yl)-thiourea 227

1-Ethyl-3-[6-(4- methyl-piperazin-1- yl)-pyrido[2,3-b]pyrazin-3-yl]-urea 228

1-Ethyl-3-[6-(4- methyl-piperazin-1- yl)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 229

1-Ethyl-3-[6-(2- methoxy-ethylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea230

1-Ethyl-3-[6-(2- methoxy-ethylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 231

1-[6- (cyclopropylmethyl- amino)-pyrido[2,3- b]pyrazin-3-yl]-3-ethyl-urea 232

1-[6- (Cyclopropylmethyl- amino)-pyrido[2,3- b]pyrazin-3-yl]-3-ethyl-thiourea 233

1-Ethyl-3-[6-(4- methyl-[1,4]diazepan- 1-yl)-pyrido[2,3-b]pyrazin-3-yl]-urea 234

1-Ethyl-3-[6-(4- methyl-[1,4]diazepan- 1-yl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 235

1-Ethyl-3-[6-(4- hydroxy-piperidin-1- yl)-pyrido[2,3-b]pyrazin-3-yl]-urea 236

1-Ethyl-3-[6-(4- hydroxy-piperidin-1- yl)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 237

1-Ethyl-3-{6-[4-(4- hydroxy-3-methoxy- phenyl)-piperazin-1-yl]-pyrido[2,3- b]pyrazin-3-yl}-urea 238

1-Ethyl-3-{6-[4-(4- hydroxy-3-methoxy- phenyl)-piperazin-1-yl]-pyrido[2,3- b]pyrazin-3-yl}- thiourea 239

1-(6-Benzylamino- pyrido[2,3-b]pyrazin- 3-yl)-3-ethyl-urea 240

1-(6-Benzylamino- pyrido[2,3-b]pyrazin- 3-yl)-3-ethyl-thiourea 241

1-Ethyl-3-[6-(4- methyl-benzylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea242

1-Ethyl-3-[6-(4- methyl-benzylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 243

1-Ethyl-3-[6-(pyridin- 3-ylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea 244

1-Ethyl-3-[6-(pyridin- 3-ylamino)- pyrido[2,3-b]pyrazin- 3-yl]-thiourea245

1-Ethyl-3-[6-(pyridin- 4-ylamino)- pyrido[2,3-b]pyrazin- 3-yl]-urea 246

1-Ethyl-3-[6-(pyridin- 4-ylamino)- pyrido[2,3-b]pyrazin- 3-yl]-thiourea247

1-Ethyl-3-(6- phenethylamino- pyrido[2,3-b]pyrazin- 3-yl)-urea 248

1-Ethyl-3-(6- phenethylamino- pyrido[2,3-b]pyrazin- 3-yl)-thiourea 249

1-Ethyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-2-yl]-urea 250

1-Ethyl-3-[7-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-2-yl]-urea 251

1-Ethyl-3-[8-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-2-yl]-urea 252

1-Ethyl-3-[7-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 253

1-Ethyl-3-[8-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 254

1-{6-[4-(Cyano- dimethyl-methyl)- phenylamino]- pyrido[2,3-b]pyrazin-3-yl}-3-ethyl-urea 255

1-{6-[4-(Cyano- dimethyl-methyl)- phenylamino]- pyrido[2,3-b]pyrazin-3-yl}-3-ethyl-thiourea 256

1-{6-[4-(1-Cyano- cyclopentyl)- phenylamino]- pyrido[2,3-b]pyrazin-3-yl}-3-ethyl-urea 257

1-{6-[4-(1-Cyano- cyclopentyl)- phenylamino]- pyrido[2,3-b]pyrazin-3-yl}-3-ethyl-thiourea 258

1-[4-(Cyano-dimethyl- methyl)-phenyl]-3-[6- (4-hydroxy-3-methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea 259

1-[4-(Cyano-dimethyl- methyl)-phenyl]-3-[6- (4-hydroxy-3-methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-thiourea 260

1-[4-(1-Cyano- cyclopentyl)-phenyl]- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 261

1-[4-(1-Cyano- cyclopentyl)-phenyl]- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-thiourea 262

[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-carbamicacid ethyl ester 263

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-propionamidine 264

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-methyl- benzamidine 265

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-furan-2-carboxamidine 266

2-(4-Chloro-phenyl)- N-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-acetamidine 267

4-Bromo-N-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-benzamidine 268

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-2-phenyl- acetamidine 269

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-methoxy- benzamidine 270

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-benzamidine 271

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-nicotinamidine 272

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-cyclohexanecarbox- amidine 273

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-methylamino- propionamidine 274

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-quinoline-3- carboxamidine 275

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-methanesulfonamide 276

4-Fluoro-N-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- benzenesulfonamide 277

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-methyl- benzenesulfonamide 278

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-carboxy- benzenesulfonamide 279

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-2,5-dimethoxy- benzenesulfonamide 280

C,C,C-Trifluoro-N-[6- (4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]- methanesulfonamide 281

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-methoxy- benzenesulfonamide 282

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-benzenesulfonamide 283

Quinoline-8-sulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 284

5-Dimethylamino- naphthalene-1- sulfonicacid[6-(4- hydroxy-3-methoxy-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-amide 285

2-Chloro- ethanesulfonic acid[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 286

2-Morphloin-4-yl- ethanesulfonicacid[6- (4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 287

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3,4-dimethoxy- benzenesulfonamide 288

2-(2,2,2-Trifluoro- acetyl)-1,2,3,4- tetrahydro- isoquinoline-7-sulfonic acid [6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-amide 289

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-3,5-bis-trifluoromethyl- benzenesulfonamide 290

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-4-trifluoromethoxy- benzenesulfonamide 291

Cyclopropanesulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 292

Cyclohexanesulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 293

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-methyl- benzenesulfonamide 294

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-C-phenyl- methanesulfonamide 295

(E)-2-Phenyl- ethenesulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 296

Hexane-1-sulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 297

Propane-1-sulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 298

Ethanesulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 299

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-isopropyl- benzenesulfonamide 300

3-{4-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-ylsulfamoyl]- phenyl}-propionic acid 301

C-Cyclopentyl-N-[6- (4-hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]- methanesulfonamide 302

Prop-2-ene-1-sulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 303

Pyridine-2-sulfonic acid [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 304

N-Ethyl-N′-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- guanidine 305

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-butyramide 306

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-benzamide 307

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-2-phenyl- acetamide 308

But-3-enoic acid [6- (4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 309

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenyl- propionamide 310

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-nicotinamide 311

Cyclohexanecarbox- ylic acid [6-(4- hydroxy-3-methoxy-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-amide 312

But-3-enoic acid [6- (4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 313

Sodium; 2-chloro-4- [3-(3-ethyl-ureido)- pyrido[2,3-b]pyrazin-6-yl]-6-methoxy- phenolate 314

1-Allyl-3-[6-(4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-thiourea315

Phosphoric acid mono-{4-[3-(3-ethyl- ureido)-pyrido[2,3-b]pyrazin-6-yl]-2- methoxy-phenyl} es- ter 316

Carbonic acid 4-[3-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin- 6-yl]-phenylester 2- methoxy-ethyl ester 317

1-Ethyl-3-{6-[4-(3- ethyl-ureido)-phenyl]- pyrido[2,3-b]pyrazin-3-yl}-urea 318

N-{5-[3-(3-Ethyl- ureido)-pyrido[2,3- b]pyrazin-6-ylamino]-2-methyl-phenyl}- methanesulfonamid 319

N-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-2-methylamino- acetamide 320

1-Ethyl-3-[2-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 321

1-Ethyl-3-[2-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 322

1-Ethyl-3-[3-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-2-yl]-urea 323

1-Ethyl-3-[3-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3- b]pyrazin-2-yl]-thiourea 324

1-Ethyl-3-(2-p- tolylamino-pyrido[2,3- b]pyrazin-3-yl)-urea 325

1-Ethyl-3-(3-p- tolylamino-pyrido[2,3- b]pyrazin-2-yl)-urea 326

N-[2-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-4-methyl- benzenesulfonamide 327

N-[3-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-2-yl]-4-methyl- benzenesulfonamide 328

N-Ethyl-N′-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- oxalamide 329

1-[3-(3-Chloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 330

1-Ethyl-3-[3-(3- phenoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 331

1-Ethyl-3-[3-(4- hydroxy-3-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 332

1-Ethyl-3-[3-(2- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 333

1-[3-(3-Acertyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 334

1-Ethyl-3-[3-(3- hydroxymethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 335

1-[3-(4- Dimethylamino- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 336

1-[3-(5-tert-Butyl-2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 337

1-[3-(5-tert-Butyl-2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 338

1-Ethyl-3-[3-(4- hydroxy-biphenyl-3- ylamino)-pyrido[2,3-b]pyrazin-6-yl]-urea 339

1-Ethyl-3-[3-(4- hydroxy-biphenyl-3- ylamino)-pyrido[2,3-b]pyrazin-6-yl]- thiourea 340

1-Ethyl-3-[3-(2′- hydroxy- [1,1′;3′,1″]terphenyl- 5′-ylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 341

1-Ethyl-3-[3-(2′- hydroxy- [1,1′;3′,1″]terphenyl- 5′-ylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 342

1-Ethyl-3-[3-(2-nitro- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea343

1-Ethyl-3-[3-(2-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 344

1-[3-(Biphenyl-2- ylmino)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 345

1-[3-(Biphenyl-2- ylamino)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-thiourea346

1-[3-(2-Acetyl- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-ethyl-urea347

1-[3-(2-Acetyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 348

1-Ethyl-3-[3-(2- isopropyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 349

1-Ethyl-3-[3-(2- isopropyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 350

1-Ethyl-3-[3-(2- trifluoromethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 351

1-Ethyl-3-[3-(2- trifluoromethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 352

1-Ethyl-3-[3-(2- morpholin-4-yl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 353

1-Ethyl-3-[3-(2- morpholin-4-yl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 354

1-Ethyl-3-[3-(2- ethynyl- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea355

1-Ethyl-3-[3-(2- ethynyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 356

1-Ethyl-3-[3-(3-nitro- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea357

1-Ethyl-3-[3-(3-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 358

3-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]- benzamidine 359

3-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzamidine 360

2-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzoic acidmethyl ester 361

2-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzoicacid methyl ester 362

4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzoic acidethyl ester 363

4-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzoicacid ethyl ester 364

1-[3-(Biphenyl-4- ylamino)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-urea 365

1-[3-(Biphenyl-4- ylamino)-pyrido[2,3- b]pyrazin-6-yl]-3- ethyl-thiourea366

1-Ethyl-3-[3-(4- trifluoromethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 367

1-Ethyl-3-[3-(4- trifluoromethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 368

{4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzyl}-phosphonic acid di- ethyl ester 369

{4-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzyl}-phosphonic acid di- ethyl ester 370

{4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-phenyl}- aceticacid 371

{4-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-phenyl}-acetic acid 372

1-[3-(2,3-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 373

1-[3-(2,3-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 374

1-[3-(3- Dimethylamino- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 375

1-[3-(3- Dimethylamino- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 376

1-Ethyl-3-[3-(2- methyl-3-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 377

1-Ethyl-3-[3-(2- methyl-3-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 378

1-[3-(2,3-Dimethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 379

1-[3-(2,3-Dimethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 380

1-Ethyl-3-[3-(3- hydroxy-2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 381

1-Ethyl-3-[3-(3- hydroxy-2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 382

2-Chloro-6-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 383

2-Chloro-6-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 384

1-Ethyl-3-[3-(2-fluoro- 3-trifluoromethyl- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 385

1-Ethyl-3-[3-(2-fluoro- 3-trifluoromethyl- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 386

1-Ethyl-3-[3-(3- hydroxymethyl-2- methyl-phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 387

1-Ethyl-3-[3-(3- hydroxymethyl-2- methyl-phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 388

1-Ethyl-3-[3-(4- methoxy-2-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 389

1-Ethyl-3-[3-(4- methoxy-2-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 390

1-[3-(2-Bromo-4- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 391

1-[3-(2-Bromo-4- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 392

1-[3-(4-Chloro-2- trifluoromethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 393

1-[3-(4-Chloro-2- trifluoromethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 394

1-Ethyl-3-[3-(4- hydroxy-2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 395

1-Ethyl-3-[3-(4- hydroxy-2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 396

1-[3-(5-Chloro-2- hydroxymethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 397

1-[3-(5-Chloro-2- hydroxymethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 398

1-[3-(2,4-Dimethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 399

1-[3-(2,4-Dimethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 400

1-Ethyl-3-[3-(2-fluoro- 5-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 401

1-Ethyl-3-[3-(2-fluoro- 5-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 402

1-[3-(2,5-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 403

1-[3-(2,5-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 404

4-Chloro-3-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 405

4-Chloro-3-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 406

1-[3-(5-Chloro-2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 407

1-[3-(5-Chloro-2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 408

1-[3-(5-tert-Butyl-2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 409

1-[3-(5-tert-Butyl-2- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin6-yl]-3-ethyl-thiourea 410

1-Ethyl-3-[3-(5-fluoro- 2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 411

1-Ethyl-3-[3-(5-fluoro- 2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 412

1-[3-(2-Chloro-5- cyano-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 413

1-[3-(2-Chloro-5- cyano-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 414

1-[3-(5-Chloro-2- phenoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 415

1-[3-(5-Chloro-2- phenoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 416

4-Chloro-3-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzamide 417

4-Chloro-3-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzamide 418

1-Ethyl-3-[3-(4- hydroxy-biphenyl-3- ylamino)-pyrido[2,3-b]pyrazin-6-yl]-urea 419

1-Ethyl-3-[3-(4- hydroxy-biphenyl-3- ylamino)-pyrido[2,3-b]pyrazin-6-yl]- thiourea 420

1-[3-(2-Cyano-5- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 421

1-[3-(2-Cyano-5- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 422

1-[3-(2-Chloro-5- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 423

1-[3-(2-Chloro-5- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 424

1-[3-(2-Chloro-6- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 425

1-[3-(2-Chloro-6- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 426

2-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-3-hydroxy-benzoic acid 427

2-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-3-hydroxy-benzoic acid 428

1-Ethyl-3-[3-(2- methyl-6-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 429

1-Ethyl-3-[3-(2- methyl-6-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 430

1-Ethyl-3-[3-(2- hydroxymethyl-6- methyl-phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 431

1-Ethyl-3-[3-(2- hydroxymethyl-6- methyl-phenylamino)-pyrido[2,3-b]pyrain- 6-yl]-thiourea 432

1-[3-(3,4-Difluoro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 433

1-[3-(3,4-Difluoro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 434

2-Chloro-5-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 435

2-Chloro-5-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 436

1-[3-(3-Cyano-4- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 437

1-[3-(3-Cyano-4- methyl-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 438

2-Chloro-5-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzenesulfonic acid 439

2-Chloro-5-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzenesulfonic acid 440

1-[3-(3-Chloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 441

1-[3-(3-Chloro-4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 442

1-[3-(3,5-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 443

1-[3-(3,5-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 444

2,5-Dichloro-3-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 445

2,5-Dichloro-3-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 446

1-Ethyl-3-[3-(4- hydroxy-2,5-dimethyl- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 447

1-Ethyl-3-[3-(4- hydroxy-2,5-dimethyl- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 448

2-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-4,5-dimethoxy-benzoic acid 449

2-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-4,5-dimethoxy-benzoic acid 450

1-[3-(2,5-Dichloro-4- nitro-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 451

1-[3-(2,5-Dichloro-4- nitro-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 452

1-[3-(2,4-Dichloro-5- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 453

1-[3-(2,4-Dichlorro-5- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 454

1-Ethyl-3-[3-(2,4,6- trichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 455

1-Ethyl-3-[3-(2,4,6- trichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 456

1-Ethyl-3-[3-(2,4,6- trimethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 457

1-Ethyl-3-[3-(2,4,6- trimethyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 458

1-[3-(2-Bromo-4,6- difluoro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 459

1-[3-(2-Bromo-4,6- difluoro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 460

1-[3-(2-Chloro-6- cyano-4-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 461

1-[3-(2-Chloro-6- cyano-4-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 462

1-[3-(4-Acetyl-2,6- dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 463

1-[3-(4-Acetyl-2,6- dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 464

1-Ethyl-3-[3-(3,4,5- trichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 465

1-Ethyl-3-[3-(3,4,5- trichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 466

1-[3-(4-Acetyl- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-ethyl-urea467

1-[3-(4-Acetyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 468

1-Ethyl-3-[3-(2- hydroxy-4-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 469

1-Ethyl-3-[3-(2- hydroxy-4-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 470

1-Ethyl-3-[3-(4- methoxy-2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 471

1-Ethyl-3-[3-(4- methoxy-2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 472

5-Bromo-2-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-benzoicacid methyl ester 473

5-Bromo-2-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid methyl ester 474

2-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-5-hydroxy-benzoic acid 475

2-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-5-hydroxy-benzoic acid 476

1-Ethyl-3-[3-(4- methyl-2-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 477

1-Ethyl-3-[3-(4- methyl-2-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 478

1-Ethyl-3-[3-(5-fluoro- 2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 479

1-Ethyl-3-[3-(5-fluoro- 2-methyl- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiorea 480

3-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-4-hydroxy-benzoic acid 481

3-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-4-hydroxy-benzoic acid 482

1-[3-(2,6-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 483

1-[3-(2,6-Dichloro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 484

2-Chloro-4-[6-(3- ethyl-ureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 485

2-Chloro-4-[6-(3- ethyl-thioureido)- pyrido[2,3-b]pyrazin-3-ylamino]-benzoic acid 486

4-[6-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-2-hydroxy-benzoic acid 487

4-[6-(3-Ethyl- thioureido)- pyrido[2,3-b]pyrazin- 3-ylamino]-2-hydroxy-benzoic acid 488

1-Ethyl-3-[3-(4-fluoro- 3-nitro-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 489

1-Ethyl-3-[3-(4-fluoro- 3-nitro-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 490

1-Ethyl-3-[3-(4- hydroxy-3-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 491

1-Ethyl-3-[3-(4- hydroxy-3-nitro- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 492

1-[3-(4,5-Dimethyl-2- nitro-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-urea 493

1-[3-(4,5-Dimethyl-2- nitro-phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-ethyl-thiourea 494

1-[3-(4-Hydroxy-3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-propyl-urea 495

1-[3-(4-Hydroxy-3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-propyl- thiourea 496

1-[3-(3-Hydroxy-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-propyl-urea 497

1-[3-(3-Hydroxy-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-propyl- thiourea 498

1-[3-(4-Hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-propyl-urea499

1-[3-(4-Hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-propyl-thiourea 500

1-Propyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 501

1-Propyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 502

1-Cyclopentyl-3-[3-(4- hydroxy-3-methoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 503

1-Cyclopentyl-3-[3-(4- hydroxy-3-methoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 504

1-Cyclopentyl-3-[3-(3- hydroxy-4-methoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 505

1-Cyclopentyl-3-[3-(3- hydroxy-4-methoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 506

1-Cyclopentyl-3-[3-(4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 507

1-Cyclopentyl-3-[3-(4- hydroxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 508

1-Cyclopentyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 509

1-Cyclopentyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 510

1-[3-(4-Hydroxy-3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-phenyl-urea 511

1-[3-(4-Hydroxy-3- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-phenyl- thiourea 512

1-[3-(3-Hydroxy-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-phenyl-urea 513

1-[3-(3-Hydroxy-4- methoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-3-phenyl- thiourea 514

1-[3-(4-Hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-phenyl-urea515

1-[3-(4-Hydroxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-3-phenyl-thiourea 516

1-Phenyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-urea 517

1-Phenyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 518

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-propyl- thiourea 519

1-Cyclopentyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 520

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenyl- thiourea 521

1-Allyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-thiourea 522

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenethyl- thiourea 523

1-Benzyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 524

1-Cyclohexyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 525

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-isopropyl- thiourea 526

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-methyl- thiourea 527

[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-thiourea528

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-pyridin-4-yl- thiourea 529

1-(4-Chloro-phenyl)- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 530

1-(4-Chloro-phenyl)- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-thiourea 531

1-(3,4-Dichloro- phenyl)-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 532

1-(3,4-Dichloro- phenyl)-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 533

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-p-tolyl-urea 534

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-p-tolyl- thiourea 535

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(3-methoxy- phenyl)-urea 536

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(3-methoxy- phenyl)-thiourea 537

2-{3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-ureido}-benzoic acid methyl ester 538

2-{3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-thioureido}- benzoic acid methyl ester 539

1-(2-Chloro-phenyl)- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 540

1-(2-Chloro-phenyl)- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-thiourea 541

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-3-(4-trifluoromethyl- phenyl)-urea 542

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-3-(4-trifluoromethyl- phenyl)-thiourea 543

1-(3,5-Dimethyl- phenyl)-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 544

1-(3,5-Dimethyl- phenyl)-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 545

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(2,4,6- trichloro-phenyl)-urea 546

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(2,4,6- trichloro-phenyl)- thiourea 547

1-(2-Fluoro-5-methyl- phenyl)-3-[6-(4- hydroxy-3-methoxy-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-urea 548

1-(2-Fluoro-5-methyl- phenyl)-3-[6-(4- hydroxy-3-methoxy-phenyl)-pyrido[2,3- b]pyrazin-3-yl]- thiourea 549

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-naphthalen-1- yl-urea 550

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-naphthalen-1- yl-thiourea 551

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-propyl-urea 552

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-isopropyl-urea 553

1-tert-Butyl-3-[6-(3,5- dichloro-4-hydroxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 554

1-tert-Butyl-3-[6-(3,5- dichloro-4-hydroxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 555

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-3-(4-dimethylamino- phenyl)-urea 556

1-Cyclooctyl-3-[6-(3,5- dichloro-4-hydroxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 557

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-methyl-urea 558

1-Cyclohexyl-3-[6- (3,5-dichloro-4- hydroxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 559

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(4-fluoro- phenyl)-urea 560

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-thiophen-2-yl- urea 561

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(2-nitro- phenyl)-urea 562

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(3,5-dimethyl- isoxazol-4-yl)-urea 563

1-Cyclopentyl-3-[6- (3,5-dichloro-4- hydroxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 564

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenethyl-urea 565

1-[6-(3,5-Dichloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-[4-(2,5-dioxo- 2,5-dihydro-pyrrol-1- yl)-phenyl]-urea 566

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3- methyl-urea567

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-isopropyl-urea 568

1-tert-Butyl-3-[6-(3,4- dimethoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-urea 569

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-(4-dimethylamino- phenyl)-urea 570

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3- propyl-urea571

1-Cyclohexyl-3-[6- (3,4-dimethoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 572

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-(4-fluoro-phenyl)-urea 573

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-(3,5-dimethyl-isoxazol-4- yl)-urea 574

[6-(4-Benzyloxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea 575

1-Allyl-3-[6-(3,4- dimethoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea576

1-Cyclopentyl-3-[6- (3,4-dimethoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 577

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-phenethyl-urea 578

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-p- tolyl-urea579

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-[4-(2,5-dioxo-2,5- dihydro-pyrrol-1-yl)- phenyl]-urea 580

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3- phenyl-urea581

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-[1-(2,2,2-trifluoro-acetyl)- piperidin-4-yl]-urea 582

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-1,3-diethyl-urea 583

1-Ethyl-3-[6-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 584

1-(4-Dimethylamino- phenyl)-3-[6-(4- hydroxy-3,5-dimethyl-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-urea 585

1-Cyclohexyl-3-[6-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 586

1-Ethyl-3-[6-(4- methoxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 587

1-Allyl-3-[6-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 588

1-[6-(4-Hydroxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenethyl-urea 589

1-[6-(4-Hydroxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-[1-(2,2,2- trifluoro-acetyl)- piperidin-4-yl]-urea 590

1-(3,5-Dimethyl- isoxazol-4-yl)-3-[6-(4- hydroxy-3,5-dimethyl-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-urea 591

1-[6-(4-Hydroxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-methyl-urea 592

1-[6-(4-Hydroxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-isopropyl-urea 593

1-tert-Butyl-3-[6-(4- hydroxy-3,5-dimethyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 594

1-(4-Fluoro-phenyl)-3- [6-(4-hydroxy-3,5- dimethyl-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 595

1-[6-(4-Hydroxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-phenyl-urea 596

1-[6-(3,5-Di-tert-butyl- 4-hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 597

1-Ethyl-3-[6-(4- isopropoxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-urea 598

1-[6-(3,5-Dimethyl-4- propoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 599

1-[6-(4-Butoxy-3,5- dimethyl-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 600

1-(4-Fluoro-phenyl)-3- [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 601

4-{3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-ureido}-benzoic acid ethyl ester 602

1-(4-Dimethylamino- phenyl)-3-[6-(4- hydroxy-3-methoxy-phenyl)-pyrido[2,3- b]pyrazin-3-yl]-urea 603

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-((1R,2S)-2- phenyl-cyclopropyl)- urea 604

1-Cyclooctyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-ul]-urea 605

1-Adamantan-1-yl-3- [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 606

4-{3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-ureido}- piperidine-1- carboxylic acid benzyl ester 607

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(2-morpholin-4- yl-pyridin-4-yl)-urea 608

1-Cycloheptyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 609

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-thiophen-2-yl- urea 610

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-[1-(2,2,2- trifluoro-acetyl)- piperidin-3-yl]-urea 611

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-pyridin-3-yl- urea 612

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(4-methyl- cyclohexyl)-urea 613

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-1-(1,1,3,3- tetramethyl-butyl)- urea 614

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-thiophen-2-yl- urea 615

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(4-piperidin-1- yl-phenyl)-urea 616

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(4-nitro- phenyl)-urea 617

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(2-nitro- phenyl)-urea 618

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(3-nitro- phenyl)-urea 619

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(3-pyrrol-1-yl- phenyl)-urea 620

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-[4-(4-methyl- piperazin-1-yl)- phenyl]-urea 621

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(1-methyl-1H- indol-4-yl)-urea 622

1-[4-(2,5-Dioxo-2,5- dihydro-pyrrol-1-yl)- phenyl]-3-[6-(4-hydroxy-4-methoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-urea 623

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(4-pyrrol-1-yl- phenyl)-urea 624

1-(4-Ethoxy-phenyl)- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 625

1-(4-methoxy-phenyl)- 3-[6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 626

1-(4-Cyano-phenyl)-3- [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 627

1-Hexyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 628

1-Cyclododecyl-3-[6- (4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-urea 629

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(3-phenyl- propyl)-urea 630

1-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-(4-phenyl- butyl)-urea 631

1-Butyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 632

1,1-Diethyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 633

3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-1,1-diphenyl- urea 634

3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-1-methyl-1-(4- trifluoromethyl- phenyl)-urea 635

3-[6-(4-Hydroxy-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-1-(4-isopropyl- phenyl)-1-methyl-urea 636

1-(4-Chloro-phenyl)-3- [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-1-methyl-urea 637

1-[6-(3-Chloro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 638

1-Ethyl-3-[6-(3- hydroxy-4-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 639

1-[6-(3-Bromo-2- methoxy-5-methyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl- urea 640

1-Ethyl-3-[6-(3-fluoro- 4-trifluoromethoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea 641

1-[6-(3-Bromo-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 642

1-[6-(3-Chloro-4- hydroxy-5-methyl- phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl- urea 643

1-[6-(3,5-Di-tert-butyl- 4-hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 644

4-[3-(3-Ethyl-ureido)- pyrido[2,3-b]pyrazin- 6-yl]-2-hydroxy- benzoicacid methyl ester 645

1-[6-(3,5-Di-bromo-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 646

1-[6-(3,5-Di-fluoro-4- hydroxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 647

1-Ethyl-3-(6-phenyl- pyrido[2,3-b]pyrazin- 3-yl)-thiourea 648

1-[6-(4-Amino-3- methoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-thiourea 649

1-Ethyl-3-[6-(3- isopropoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 650

1-Ethyl-3-[6-(3,4,5- trimethoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 651

1-Ethyl-3-(6-p-tolyl- pyrido[2,3-b]pyrazin- 3-yl)-thiourea 652

1-tert-Butyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 653

1-Cyclooctyl-3-[6-(4- hydroxy-3-methoxy- phenyl)-pyrido[2,3-b]pyrazin-3-yl]- thiourea 654

1-Adamantan-1-yl-3- [6-(4-hydroxy-3- methoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-thiourea 655

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-2-yl]-3-ethyl- urea656

1-[7-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-2-yl]-3-ethyl- urea657

1-[8-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-2-yl]-3-ethyl- urea658

1-Ethyl-3-[7-(3,4- Dimethoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea659

1-Ethyl-3-[8-(3,4- Dimethoxy-phenyl)- pyrido[2,3-b]pyrazin- 3-yl]-urea660

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- benzamide 661

Cyclohexanecarbox- ylic acid [6-(3,4- dimethoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 662

[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- carbamic acidethyl ester 663

N-[6-(3,3-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- propionamide664

[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- carbamic acidphenyl ester 665

[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- carbamic acidbenzyl ester 666

[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- carbamic acidallyl ester 667

[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- carbamic acidmethyl ester 668

[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- carbamic acidcyclopentyl ester 669

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-benzenesulfonamide 670

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-C- phenyl-methanesulfonamide 671

Cyclohexanesulfonic acid [6-(3,4- dimethoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 672

Hexane-1-sulfonic acid [6-(3,4- dimethoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-amide 673

Prop-2-ene-1-sulfonic acid [6-(3,4- dimethoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 674

Cyclopropanesulfonic acid [6-(3,4- dimethoxy-phenyl)-pyrido[2,3-b]pyrazin- 3-yl]-amide 675

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-4- methyl-benzenesulfonamide 676

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- acetamidine677

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- benzamidine678

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-cyclohexanecarbox- amidine 679

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-2,2- dimethyl-propionamidine 680

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-isobutyramidine 681

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-2-phenyl-acetamidine 682

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-4-hydroxy-benzamidine 683

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]- guanidine 684

N-Cyclohexyl-N′-[6- (3,4-dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-guanidine 685

N-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-N′-ethyl-guanidine 686

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-ethyl-1-methyl-urea 687

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-1,3,3-trimethyl-urea 688

1-Benzyl-1-[6-(3,4- dimethoxy-phenyl)- pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea 689

1-[6-(3,4-Dimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3-yl]-3-ethyl-1-phenethyl-urea 690

1-Cyclohexyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 691

1-Cyclooctyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 692

1-Methyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 693

1-Allyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 694

1-tert-Butyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 695

1-(3,5-Dimethyl- isoxazol-4-yl)-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 696

1-Cyclohexylmethyl-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 697

1-Benzyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 698

1-(4-methyl-benzyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 699

1-Phenethyl-3-[3- (3,4,5-trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 700

1-(2-Piperidin-1-yl- ethyl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 701

1-(4-Fluoro-benzyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 702

1-Pentyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 703

1-(2-Morpholin-4-yl- ethyl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 704

1-(3-Phenyl-propyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 705

1-(2-Methoxy-ethyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 706

1-Ethyl-3-{3-[methyl- (3,4,5-trimethoxy- phenyl)-amino]-pyrido[2,3-b]pyrazin- 6-yl}-thiourea 707

1-Cyclopropyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 708

1-Furan-2-ylmethyl-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 709

3-{3-[3-(3,4,5- Trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thioureido}- propionic acid ethyl ester 710

1-(3-Methoxy-propyl)- 3-[3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 711

1-(1-Phenyl-ethyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 712

1-(1,1,3,3- Tetramethyl-butyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 713

1-Prop-2-ynyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]thiourea 714

1-(1-Ethyl-propyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 715

1-(2-Chloro-ethyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 716

1-(2-Bromo-ethyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 717

1-Methoxymethyl-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 718

1-Cyclopropylmethyl- 3-[3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 719

1-(3-Diethylamino- propyl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 720

1-Ethyl-3-[2-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 721

1-Ethyl-3-[2-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-7-yl]-thiourea 722

1-Ethyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-7-yl]-thiourea 723

1-Ethyl-3-[2-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-8-yl]-thiourea 724

1-Ethyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-8-yl]-thiourea 725

1-Ethyl-3-[2-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-3-yl]-thiourea 726

1-Ethyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-2-yl]-thiourea 727

1-Ethyl-1-methyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 728

3-Ethyl-1-methyl-1-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 729

1-Ethyl-1,3-dimethyl- 3-[3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 730

1-Ethyl-1,3-dimethyl- 3-{3-[methyl-(3,4,5- trimethoxy-phenyl)-amino]-pyrido[2,3- b]pyrazin-6-yl}- thiourea 731

N-[3-(3,4,5- Trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-propionamide 732

N-[3-(3,4,5- Trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-benzamide 733

N*6*-Ethyl-N*3*- (3,4,5-trimethoxy- phenyl)-pyrido[2,3- b]pyrazin-3,6-diamine 734

N-[3-(3,4,5- Trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-benzenesulfonamide 735

Cyclohexanesulfonic acid [3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-amide 736

Propane-1-sulfonic acid [3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-amide 737

N-Ethyl-N′-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-guanidine 738

1-Phenyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 739

1-(4-Fluoro-phenyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 740

1-(3-Methyl-benzyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 741

1-(3-Methoxy-benzyl)- 3-[3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 742

1-(3-Fluoro-benzyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 743

1-(3-Chloro-benzyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]thiourea 744

1-(2-Methyl-benzyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 745

1-(2-Fluoro-benzyl)-3- [3-(3,4,5-trimethoxy- benzylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 746

1-(2-Chloro-benzyl)-3- [3-(3,4,5-trimerthoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 747

1-(2-Methoxy-benzyl)- 3-[3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 748

1-(3,4-Dimethoxy- benzyl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 749

1-(2,3-Dimethoxy- benzyl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 750

1-Benzo[1,3]dioxol-5- ylmethyl-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 751

1-(3,4-Dichloro- benzyl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 752

1-(2-Fluoro-propyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 753

1-(3-Fluoro-propyl)-3- [3-(3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 754

1-(2-Fluoro- cyclobutyl)-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 755

1-Cyclobutyl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 756

1-(2-Fluoro- cyclopentyl)-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 757

1-(2-Fluoro- cyclohexyl)-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 758

1-Piperidin-4-yl-3-[3- (3,4,5-trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 759

1-(1-Methyl-piperidin- 4-yl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 760

1-(3-Fluoro-piperidin- 4-yl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 761

1-(3-Fluoro-1-methyl- piperidin-4-yl)-3-[3- (3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-thiourea 762

[3-(3,4,5-Trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-thiourea763

1-Octyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 764

1-Decyl-3-[3-(3,4,5- trimethoxy- phenylamino)- pyrido[2,3-b]pyrazin-6-yl]-thiourea 765

1-Ethyl-3-{3-[methyl- (3,4,5-trimethoxy- phenyl)-amino]-pyrido[2,3-b]pyrazin- 6-yl}-thiourea 766

Namensgebung mit Autonom nicht möglich 767

1-(1-Oxy-piperidin-4- yl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-thiourea 768

1-(1-Methyl-1-oxy- piperidin-4-yl)-3-[3- (3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-thiourea 769

1-(3-Fluoro-1-oxy- piperidin-4-yl)-3-[3- (3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-thiourea 770

1-(3-Fluoro-1-methyl- 1-oxy-piperidin-4-yl)- 3-[3-(3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-thiourea 771

1-(1-Oxy-piperidin-4- yl)-3-[3-(3,4,5- trimethoxy- phenylamino)-pyrido[2,3-b]pyrazin- 6-yl]-urea 772

1-(1-Methyl-1-oxy- piperidin-4-yl)-3-[3- (3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea 773

1-(3-Fluoro-1-oxy- piperidin-4-yl)-3-[3- (3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-urea 774

1-(3-Fluoro-1-methyl- 1-oxy-piperidin-4-yl)- 3-[3-(3,4,5-trimethoxy-phenylamino)- pyrido[2,3-b]pyrazin- 6-yl]-ureaFor the avoidance of doubt, if chemical name and chemical structure ofthe above illustrated compounds do not correspond by mistake, thechemical structure is regarded to unambigously define the compound.

All the above generically or explicitly disclosed pyrido[2,3-b]pyrazinederivatives, including preferred subsets/embodiments of general formula(I) and Compounds 1 to 774 are hereinafter referred to as compounds ofthe (present) invention.

The terms indicated for explanation of the above compounds of theinvention always, unless indicated otherwise in the description or inthe claims, have the following meanings:

The term “unsubstituted” means that the corresponding radical, group ormoiety has no substituents.

The term “substituted” means that the corresponding radical, group ormoiety has one or more substituents. Where a radical has a plurality ofsubstituents, and a selection of various substituents is specified, thesubstituents are selected independently of one another and do not needto be identical.

The term “alkyl” for the purposes of this invention refers to acyclicsaturated or unsaturated hydrocarbon radicals which may be branched orstraight-chain and have 1 to 8 carbon atoms, i.e. C₁₋₈-alkanyls,C₂₋₈-alkenyls and C₂₋₈-alkynyls. Alkenyls have at least one C—C doublebond and alkynyls at least one C—C triple bond. Alkynyls mayadditionally also have at least one C—C double bond. Examples ofsuitable alkyl radicals are methyl, ethyl, n-propyl, isopropyl, n-butyl,isobutyl, sec-butyl, tert-butyl, n-pentyl, iso-pentyl, neo-pentyl,tert-pentyl, 2- or 3-methyl-pentyl, n-hexyl, 2-hexyl, isohexyl,n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, n-dodecyl, n-tetradecyl,n-hexadecyl, n-octadecyl, n-icosanyl, n-docosanyl, ethylenyl (vinyl),propenyl (—CH₂CH═CH₂; —CH═CH—CH₃, —C(═CH₂)—CH₃), butenyl, pentenyl,hexenyl, heptenyl, octenyl, octadienyl, octadecenyl, octadec-9-enyl,icosenyl, icos-11-enyl, (Z)-icos-11-enyl, docosnyl, docos-13-enyl,(Z)-docos-13-enyl, ethynyl, propynyl (—CH₂—C≡CH, —C≡C—CH₃), butynyl,pentynyl, hexynyl, heptynyl, octynyl.

The term “(C₉-C₃₀)alkyl” for the purposes of this invention refers toacyclic saturated or unsaturated hydrocarbon radicals which may bebranched or straight-chain and have 9 to 30 carbon atoms, i.e.C₉₋₃₀-alkanyls, C₉₋₃₀-alkenyls and C₉₋₃₀-alkynyls. C₉₋₃₀-Alkenyls haveat least one C—C double bond and C₉₋₃₀-alkynyls at least one C—C triplebond. C₉₋₃₀-Alkynyls may additionally also have at least one C—C doublebond. Examples of suitable (C₉-C₃₀)alkyl radicals are tetradecyl,hexadecyl, octadecyl, eicosanyl, cis-13-docosenyl (erucyl),trans-13-docosenyl (brassidyl), cis-15-tetracosenyl (nervonyl) andtrans-15-tetracosenyl.

The term “cycloalkyl” for the purposes of this invention refers tosaturated and partially unsaturated non-aromatic cyclic hydrocarbongroups/radicals, having 1 to 3 rings, that contain 3 to 20, preferably 3to 12, most preferably 3 to 8 carbon atoms. The cycloalkyl radical mayalso be part of a bi- or polycyclic system, where, for example, thecycloalkyl radical is fused to an aryl, heteroaryl or heterocyclylradical as defined herein by any possible and desired ring member(s).The bonding to the compounds of the general formula (I) can be effectedvia any possible ring member of the cycloalkyl radical. Examples ofsuitable cycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl,cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, cyclohexenyl,cyclopentenyl and cyclooctadienyl.

The term “heterocyclyl” for the purposes of this invention refers to amono- or poly-cyclic system of 3 to 20, preferably 5 or 6 to 14 ringatoms comprising carbon atoms and 1, 2, 3, 4, or 5 heteroatoms, inparticular nitrogen, oxygen and/or sulfur which are identical ordifferent. The cyclic system may be saturated, mono- or polyunsaturatedbut may not be aromatic. In the case of a cyclic system consisting of atleast two rings the rings may be fused or spiro- or otherwise connected.Such “heterocyclyl” radicals can be linked via any ring member. The term“heterocyclyl” also includes systems in which the heterocycle is part ofa bi- or polycyclic saturated, partially unsaturated and/or aromaticsystem, such as where the heterocycle is fused to an “aryl”,“cycloalkyl”, “heteroaryl” or “heterocyclyl” group as defined herein viaany desired and possible ring member of the heterocycyl radical. Thebonding to the compounds of the general formula (I) can be effected viaany possible ring member of the heterocycyl radical. Examples ofsuitable “heterocyclyl” radicals are pyrrolidinyl, thiapyrrolidinyl,piperidinyl, piperazinyl, oxapiperazinyl, oxapiperidinyl, oxadiazolyl,tetrahydrofuryl, imidazolidinyl, thiazolidinyl, tetrahydropyranyl,morpholinyl, tetrahydrothiophenyl, dihydropyranyl.

The term “aryl” for the purposes of this invention refers to aromatichydrocarbon systems having 3 to 14, preferably 5 to 14, more preferably6 to 14 carbon atoms. The term “aryl” also includes systems in which thearomatic cycle is part of a bi- or poly-cyclic saturated, partiallyunsaturated and/or aromatic system, such as where the aromatic cycle isfused to an “aryl”, “cycloalkyl”, “heteroaryl” or “heterocyclyl” groupas defined herein via any desired and possible ring member of the arylradical. The bonding to the compounds of the general formula (I) can beeffected via any possible ring member of the aryl radical. Examples ofsuitable “aryl” radicals are phenyl, biphenyl, naphthyl and anthracenyl,but likewise indanyl, indenyl, or 1,2,3,4-tetrahydronaphthyl.

The term “heteroaryl” for the purposes of this invention refers to a 3to 14, preferably 5 to 14, more preferably 5-, 6- or 7-membered cyclicaromatic hydrocarbon radical which comprises at least 1, whereappropriate also 2, 3, 4 or 5 heteroatoms, preferably nitrogen, oxygenand/or sulfur, where the heteroatoms are identical or different. Thenumber of nitrogen atoms is preferably 0, 1, 2, or 3, and that of theoxygen and sulfur atoms is independently 0 or 1. The term “heteroaryl”also includes systems in which the aromatic cycle is part of a bi- orpolycyclic saturated, partially unsaturated and/or aromatic system, suchas where the aromatic cycle is fused to an “aryl”, “cycloalkyl”,“heteroaryl” or “heterocyclyl” group as defined herein via any desiredand possible ring member of the heteroaryl radical. The bonding to thecompounds of the general formula (I) can be effected via any possiblering member of the heteroaryl radical. Examples of suitable “heteroaryl”are pyrrolyl, thienyl, furyl, imidazolyl, thiazolyl, isothiazolyl,oxazolyl, oxadiazolyl, isoxazolyl, pyrazolyl, pyridinyl, pyrimidinyl,pyridazinyl, pyrazinyl, indolyl, quinolinyl, isoquinolinyl, imidazolyl,triazolyl, triazinyl, tetrazolyl, phthalazinyl, indazolyl, indolizinyl,quinoxalinyl, quinazolinyl, pteridinyl, carbazolyl, phenazinyl,phenoxazinyl, phenothiazinyl, acridinyl.

For the purposes of the present invention, the terms “alkyl-cycloalkyl”,“cycloalkylalkyl”, “alkyl-heterocyclyl”, “heterocyclylalkyl”,“alkyl-aryl”, “arylalkyl”, “alkyl-heteroaryl” and “heteroarylalkyl” meanthat alkyl, cycloalkyl, heterocycl, aryl and heteroaryl are each asdefined above, and the cycloalkyl, heterocyclyl, aryl and heteroarylradical is bonded to the compounds of the general formula (I) via analkyl radical, preferably C₁-C₈-alkyl radical, more preferablyC₁-C₄-alkyl radical.

The term “halogen”, “halogen atom” or “halogen substituent” (Hal-) forthe purposes of this invention refers to one, where appropriate, aplurality of fluorine (F, fluoro), bromine (Br, bromo), chlorine (Cl,chloro), or iodine (I, iodo) atoms. The designations “di-halogen”,“trihalogen” and “perhalogen” refer respectively to two, three and foursubstituents, where each substituent can be selected independently fromthe group consisting of fluorine, chlorine, bromine and iodine.“Halogen” preferably means a fluorine, chlorine or bromine atom.

All stereoisomers of the compounds of the invention are contemplated,either in a mixture or in pure or substantially pure form. The compoundsof the invention can have asymmetric centers at any of the carbon atoms.Consequently, they can exist in the form of their racemates, in the formof the pure enantiomers and/or diastereomers or in the form of mixturesof these enantiomers and/or diastereomers. The mixtures may have anydesired mixing ratio of the stereoisomers.

Thus, for example, the compounds of the invention which have one or morecenters of chirality and which occur as racemates or as diastereomermixtures can be fractionated by methods known per se into their opticalpure isomers, i.e. enantiomers or diastereomers. The separation of thecompounds of the invention can take place by column separation on chiralor nonchiral phases or by recrystallization from an optionally opticallyactive solvent or with use of an optically active acid or base or byderivatization with an optically active reagent such as, for example, anoptically active alcohol, and subsequent elimination of the radical.

The compounds of the invention may be present in the form of theirdouble bond isomers as “pure” E or Z isomers, or in the form of mixturesof these double bond isomers.

Where possible, the compounds of the invention may be in the form of thetautomers.

It is likewise possible for the compounds of the invention to be in theform of any desired prodrugs such as, for example, esters, carbonates,carbamates, ureas, amides, N-oxides or phosphates, in which cases theactually biologically active form is released only through metabolism.Any compound that can be converted in vivo to provide the bioactiveagent (i.e. compounds of the invention) is a prodrug within the scopeand spirit of the invention.

Various forms of prodrugs are well known in the art and are describedfor instance in:

-   (i) Wermuth C G et al., Chapter 31: 671-696, The Practice of    Medicinal Chemistry, Academic Press 1996;-   (ii) Bundgaard H, Design of Prodrugs, Elsevier 1985; and-   (iii) Bundgaard H, Chapter 5: 131-191, A Textbook of Drug Design and    Development, Harwood Academic Publishers 1991.

Said references are incorporated herein by reference.

It is further known that chemical substances are converted in the bodyinto metabolites which may where appropriate likewise elicit the desiredbiological effect—in some circumstances even in more pronounced form.

Any biologically active compound that was converted in vivo bymetabolism from any of the compounds of the invention is a metabolitewithin the scope and spirit of the invention.

Corresponding prodrugs and metabolites of the compounds of the inventionshould be considered to be part of the invention.

The compounds of the invention can, if they have a sufficiently basicgroup such as, for example, a secondary or tertiary amine, be convertedwith inorganic and organic acids into salts. The pharmaceuticallyacceptable salts of the compounds of the invention are preferably formedwith hydrochloric acid, hydrobromic acid, iodic acid, sulfuric acid,phosphoric acid, methanesulfonic acid, p-toluenesulfonic acid, carbonicacid, formic acid, acetic acid, sulfoacetic acid, trifluoroacetic acid,oxalic acid, malonic acid, maleic acid, succinic acid, tartaric acid,racemic acid, malic acid, embonic acid, mandelic acid, fumaric acid,lactic acid, citric acid, taurocholic acid, glutaric acid, stearic acid,glutamic acid or aspartic acid. The salts which are formed are, interalia, hydrochlorides, chlorided, hydrobromides, bromides, iodides,sulfates, phosphates, methanesulfonates, tosylates, carbonates,bicarbonates, formates, acetates, sulfoacetates, triflates, oxalates,malonates, maleates, succinates, tartrates, malates, embonates,mandelates, fumarates, lactates, citrates, glutarates, stearates,aspartates and glutamates. The stoichiometry of the salts formed fromthe compounds of the invention may moreover be an integral ornon-integral multiple of one.

The compounds of the invention can, if they contain a sufficientlyacidic group such as, for example, the carboxy, sulfonic acid,phosphoric acid or a phenolic group, be converted with inorganic andorganic bases into their physiologically tolerated salts. Examples ofsuitable inorganic bases are ammonium, sodium hydroxide, potassiumhydroxide, calcium hydroxide, and of organic bases are ethanolamine,diethanolamine, triethanolamine, ethylenediamine, t-butylamine,t-octylamine, dehydroabietylamine, cyclohexylamine,dibenzylethylene-diamine and lysine. The stoichiometry of the saltsformed from the compounds of the invention can moreover be an integralor non-integral multiple of one.

It is likewise possible for the compounds of the invention to be in theform of their solvates and, in particular, hydrates which can beobtained for example by crystallization from a solvent or from aqueoussolution. It is moreover possible for one, two, three or any number ofsolvate or water molecules to combine with the compounds of theinvention to give solvates and hydrates.

It is known that chemical substances form solids which exist indifferent order states which are referred to as polymorphic forms ormodifications. The various modifications of a polymorphic substance maydiffer greatly in their physical properties. The compounds of theinvention can exist in various polymorphic forms and certainmodifications may moreover be metastable. All these polymorphic forms ofthe compounds are to be regarded as belonging to the invention.

It has now been found in a surprising and advantageous manner that thecompounds of the invention can also act, i.e. have a modulating orinhibiting effect, on two or more signal transduction pathways orenzymes of such pathways. It has been found that the compounds of theinvention act, i.e. modulate or inhibit, with high selectivity.

Such a simultaneous, for example dual, modulation or inhibition of twoor more signal transduction pathways, for example ras-Raf-Mek-Erk signalpathway, PI3K-Akt signal pathway and/or SAPK signal pathway, morespecifically Erk1/Erk2 and/or PI3K and/or Jnk and/or p38, isadvantageous over the only single modulation or inhibition of one signaltransduction pathway, since synergistic therapeutic effects can bebrought about, for example enhanced apoptosis and more rapid andefficient tumor regression.

The surprising advantageous effects of the compounds of the inventionenable multiple therapeutic approaches to be pursued in thephysiological and/or pathophysiological states or conditions which aresensitive to the treatment or modulation of, or are mediated by, two ormore signal transduction pathways.

It has also been found in a surprising and advantageous manner that thecompounds of the invention can also act, i.e. have modulating orinhibiting action, with high selectivity on the ras-Raf-Mek-Erk signaltransduction pathway or enzymes thereof, and that the multiplemechanisms of action and therapeutic approaches detailed above can alsofind use with this signal pathway or enzymes.

It has also been found in a surprising and advantageous manner that thecompounds of the invention can also act, i.e. have modulating orinhibiting action, with high selectivity on the PI3K-Akt signaltransduction pathway or enzymes thereof, and that the multiplemechanisms of action and therapeutic approaches detailed above can alsofind use with this signal pathway or enzymes.

It has also been found in a surprising and advantageous manner that thecompounds of the invention can also act, i.e. have modulating orinhibiting action, with high selectivity on the SAPK signal transductionpathway or enzymes thereof, and that the multiple mechanisms of actionand therapeutic approaches detailed above can also find use with thissignal pathway or enzymes.

It has additionally been found in a surprising and advantageous mannerthat the compounds of the invention can also act, i.e. have a modulatingor inhibiting action, with high selectivity on enzymes such as ATM, ATR,mTOR, DNA-PK and/or hSMG-1, and that the multiple mechanisms of actionand therapeutic approaches detailed above can also find use with theseenzymes.

According to the invention, the term “modulation” is understood to meanthe following: “activation, partial activation, inhibition, partialinhibition”. It is within the technical knowledge of the average personskilled in the art to measure and to determine such an activation,partial activation, inhibition or partial inhibition by means of thecustomary measurement and determination methods. For example, a partialactivation can be measured and determined in relation to a fullactivation; and likewise a partial inhibition in relation to a fullinhibition.

According to the invention, the term “inhibition” is understood to meanthe following: “partial or full inhibition”. It is within the technicalknowledge of the average person skilled in the art to measure and todetermine such a partial or full inhibition by means of the customarymeasurement and determination methods. For example, partial inhibitioncan be measured and determined in relation to full inhibition.

The terms “modulation” and “inhibition” relate, in connection with“enzymes” and/or “kinases” in the context of this invention, both to theinactive form (enzymatically inactive) and/or active form (enzymaticallyactive) of the particular enzyme and/or kinase. This means in thecontext of this invention that a compound of the invention can displayits modulating action on the inactive form, active form or both forms ofthe enzyme and/or kinase.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the present invention orpharmaceutical compositions as described herein for use as a medicament.

In another aspect, the object of the present invention has surprisinglybeen solved by providing the use of the compounds of the invention orpharmaceutical compositions as described herein for the manufacture of amedicament for the treatment or prophylaxis of the physiological and/orpathological conditions described herein.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for modulating misdirected cellular signaltransduction processes, especially for influencing the function ofactive and inactive receptor tyrosine kinases, and also cytoplasmictyrosine, serine/threonine and lipid kinases, such as c-Raf, B-Raf, Mek,MAPKs, PDGFRbeta, Flt-3, IGF1R, PI3K, PKB/Akt1, c-Kit, c-Abl, FGFR1 andKDR.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals, that aremediated by one or more signal transduction pathways selected from thegroup consisting of: “ras-Raf-Mek-Erk signal transduction pathway,PI3K-Akt signal transduction pathway and/or SAPK signal transductionpathway”.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals mediatedby one or more enzymes selected from the group consisting of: “ATM, ATR,mTOR, DNA-PK, hSMG-1”.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals, where thetreatment or prophylaxis is brought about by modification of one or moreenzymes selected from the group consisting of: “ATM, ATR, mTOR, DNA-PK,hSMG-1”.

In a preferred embodiment, the compounds of the invention are providedfor use in the manufacture of a medicament for the treatment orprophylaxis of physiological and/or pathophysiological conditionsmediated by ras-Raf-Mek-Erk signal transduction pathway and PI3K-Aktsignal transduction pathway in mammals, and/or for the manufacture of amedicament for the treatment or prophylaxis of physiological and/orpathophysiological conditions in mammals, where the treatment orprophylaxis is brought about by modulation of ras-Raf-Mek-Erk signaltransduction pathway and of PI3K-Akt signal transduction pathway.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions mediated byras-Raf-Mek-Erk signal transduction pathway in mammals.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions mediated by PI3K-Aktsignal transduction pathway in mammals.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals, where thetreatment or prophylaxis is brought about by modulation of PI3K-Aktsignal transduction pathway.

In a preferred embodiment, the compounds of the invention are providedfor use in the manufacture of a medicament for the treatment orprophylaxis of physiological and/or pathophysiological conditionsmediated by SAPK signal transduction pathway and PI3K-Akt signaltransduction pathway in mammals, and/or for the manufacture of amedicament for the treatment or prophylaxis of physiological and/orpathophysiological conditions in mammals, where the treatment orprophylaxis is brought about by modulation of SAPK signal transductionpathway and of PI3K-Akt signal transduction pathway.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions mediated by SAPKsignal transduction pathway in mammals.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals, where thetreatment or prophylaxis is brought about by modulation of SAPK signaltransduction pathway.

In a preferred embodiment, the compounds of the invention are providedfor the uses detailed above, where the modulation of ras-Raf-Mek-Erksignal transduction pathway is brought about by modulation of one ormore enzymes selected from the group consisting of: “tyrosine kinase,serine/threonine kinase, receptor tyrosine kinase, cytoplasmic tyrosinekinase, cytoplasmic serine/threonine kinase” and preferably selectedfrom the group consisting of “Erk, Erk1, Erk2”.

In a further preferred embodiment, the compounds of the invention areprovided for the uses as detailed above, where the modulation ofPI3K-Akt signal transduction pathway is brought about by modulation ofone or more enzymes selected from the group consisting of “lipidkinases” and preferably selected from the group consisting of: “PI3K,PI3Kalpha, PI3 Kbeta, PI3 Kgamma, PI3 Kdelta, PI3K-C2alpha, PI3K-C2beta,PI3K-Vps34p”.

In a further preferred embodiment, the compounds of the invention areprovided for the uses as detailed above, where the modulation of SAPKsignal transduction pathway is brought about by modulation of one ormore enzymes selected from the group consisting of: “tyrosine kinase,serine/threonine kinase, receptor tyrosine kinase, cytoplasmatictyrosine kinase, cytoplasmatic serine/threonine kinase” and preferablyselected from the group consisting of: “Jnk, Jnk1, Jnk2, Jnk3, p38,p38alpha, p38beta, p38gamma, p38delta”.

In a further aspect, the object of the invention has surprisingly beensolved by providing a process of manufacturing the compounds of theinvention.

In a further aspect, the object of the invention has surprisingly beensolved by providing the compounds of the invention according to theaspects, preferred embodiments and uses detailed above for use in themanufacture of a medicament for the treatment or prophylaxis ofphysiological and/or pathophysiological conditions in mammals, where thetreatment or prophylaxis is brought about by modulation of two or moreenzymes.

In a more preferred embodiment, the compounds of the invention areprovided for the uses detailed above, where at least one enzyme in thetreatment or prophylaxis brought about by modulation of two or moreenzymes is selected from the group consisting of: “Erk, Erk1, Erk2” andat least one enzyme is selected from the group consisting of: “PI3K,PI3Kalpha, PI3 Kbeta, PI3 Kgamma, PI3 Kdelta, PI3K-C2alpha, PI3KC2beta,PI3K-Vps34p”.

In a more preferred embodiment, the compounds of the invention areprovided for the uses detailed above, where at least one enzyme in thetreatment or prophylaxis brought about by modulation of two or moreenzymes is selected from the group consisting of: “Jnk, Jnk1, Jnk2,Jnk3, p38, p38alpha, p38beta, p38gamma, p38delta” and at least oneenzyme is selected from the group consisting of: “PI3K, PI3Kalpha, PI3Kbeta, PI3 Kgamma, PI3 Kdelta, PI3K-C2alpha, PI3K-C2beta, PI3K-Vps34p”.

In a more preferred embodiment, the compounds of the invention areprovided for the uses detailed above, where at least one enzyme in thetreatment or prophylaxis brought about by modulation of two or moreenzymes is selected from the group consisting of: “Erk, Erk1, Erk2” andat least one enzyme is selected from the group consisting of: “ATM, ATR,mTOR, DNA-PK, hSMG-1”.

In a more preferred embodiment, the compounds of the invention areprovided for the uses detailed above, where at least one enzyme in thetreatment or prophylaxis brought about by modulation of two or moreenzymes is selected from the group consisting of: “Jnk, Jnk1, Jnk2,Jnk3, p38, p38alpha, p38beta, p38gamma, p38delta” and at least oneenzyme is selected from the group consisting of: “ATM, ATR, mTOR, DNAPK,hSMG-1”.

In a more preferred embodiment, the compounds of the invention areprovided for the uses detailed above, where at least one enzyme in thetreatment or prophylaxis brought about by modulation of two or moreenzymes is selected from the group consisting of: “PI3K, PI3Kalpha, PI3Kbeta, PI3 Kgamma, PI3 Kdelta, PI3K-C2alpha, PI3K-C2beta, PI3K-Vps34p”and at least one enzyme is selected from the group consisting of: “ATM,ATR, mTOR, DNA-PK, hSMG-1”.

In another preferred embodiment, the compounds of the invention areprovided for the uses detailed above, where the modulation is aninhibition.

Likewise, corresponding medicaments comprising at least one compound ofthe invention or at least one pharmaceutical composition as describedherein for use in the treatment or prophylaxis of the herein disclosedphysiological and/or pathological conditions are also comprised by thepresent invention.

For the purpose of the present invention, the compounds of the inventionmay be administered to all known mammals, especially to the human, fortreatment and/or prophylaxis.

Preferably, such mammals are selected from the group consisting of“human, domestic animals, cattle, livestock, pets, cow, sheep, pig,goat, horse, pony, donkey, hinny, mule, hare, rabbit, cat, dog, guineapig, hamster, rat, mouse”. More preferably, such mammals are human.

For the purpose of the present invention, the compounds of the inventionmay be used for the treatment or prophylaxis of all known physiologicaland/or pathophysiological conditions.

In a preferred embodiment, the compounds of the invention are providedfor the uses detailed above, where the physiological and/orpathophysiological conditions are selected from the group consisting of:“malignant tumors, benign tumors, inflammatory disorders, inflammations,pain, rheumatic disorders, arthritic disorders, HIV infections,neurological or neurodegenerative disorders, rheumatism, arthritis,AIDS, ARC (AIDS related complex), Kaposi's sarcoma, tumors originatingin the brain and/or nervous system and/or meninges (refer to WO99/01764), dementia, Alzheimer's disease, hyperproliferative disorders,psoriasis, endometriosis, scar formation, benign prostate hyperplasia(BPH), disorders of the immune system, autoimmune disorders, immunedeficiency disorders, colon tumor, stomach tumor, intestine tumor, lungtumor, pancreas tumor, ovarian tumor, prostate tumor, leukemia,melanoma, liver tumor, kidney tumor, head tumor, throat tumor, glioma,breast tumor, uterine cancer, endometrial cancer, cervical cancer, braintumor, adenocanthoma, bladder cancer, colorectal tumor, esophagealcancer, gynecological tumor, ovarian tumor, thyroid cancer, lymphoma,chronic leukemia, acute leukemia, restenosis, diabetes, diabeticnephropathy, fibrotic disorders, cystic fibrosis, malignantnephrosclerosis, thrombotic microangiopathy syndrome, organ transplantrejection, glomerulopathies, disorders of the metabolism, solid tumors,rheumatic arthritis, diabetic retinopathy, asthma, allergies, allergicdisorders, chronic obstructive pulmonary disorders, inflammatory boweldisorder, fibrosis, atherosclerosis, cardiac disorders, cardiovasculardisorders, disorders of the heart muscle, vascular disorders,angiogenetic disorders, kidney disorders, rhinitis, Grave's disease,focal ischemia, heart failure, ischemia, cardiac hypertrophy, kidneyfailure, cardiac myocyte dysfunction, high blood pressure, vascularconstriction, stroke, anaphylactic shock, blood platelet agglutination,skeletal muscular atrophy, obesity, excess weight, glucose homeostasis,congestive heart failure, angina, heart attack, myocardial infarction,hyperglycemia, hypoglycemia, hypertension”.

In a further aspect of the present invention, the object of theinvention has surprisingly been solved by providing the compounds of theinvention according to the aspects, preferred embodiments and usesdetailed above for use in the manufacture of a medicament for thetreatment or prophylaxis of physiological and/or pathophysiologicalconditions in mammals, where the medicament comprises at least onefurther pharmacologically active substance.

In a further aspect of the present invention, the object of theinvention has surprisingly been solved by providing the compounds of theinvention according to the aspects, preferred embodiments and usesdetailed above for use in the manufacture of a medicament for thetreatment or prophylaxis of physiological and/or pathophysiologicalconditions in mammals, where the medicament is administered beforeand/or during and/or after the treatment with at least one furtherpharmacologically active substance.

In a further aspect of the present invention, the object of theinvention has surprisingly been solved by providing the compounds of theinvention according to the aspects, preferred embodiments and usesdetailed above for use in the manufacture of a medicament for thetreatment or prophylaxis of physiological and/or pathophysiologicalconditions in mammals, where the medicament is administered beforeand/or during and/or after the treatment with radiation therapy and/orsurgery.

In the context of the present invention, the compounds of the inventionmay be administered with all known pharmacologically active substancesin a combination therapy as detailed.

In a preferred embodiment, the compounds of the invention are providedfor the uses detailed above, where the further pharmacologically activesubstance is selected from the group consisting of: “DNA topoisomerase Iand/or II inhibitors, DNA intercalators, alkylating agents, microtubulidestabilizers, hormone and/or growth factor receptor agonists and/orantagonists, antibodies against growth factors and their receptors,kinase inhibitors, antimetabolites”.

In a preferred embodiment, the compounds of the invention are providedfor the above uses, where the further pharmacologically active substanceis selected from the group consisting of: “asparaginase, bleomycin,carboplatin, carmustine, chlorambucil, cisplatin, colaspase,cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin,doxorubicin (adriamycin), epirubicin, etoposide, 5-fluorouracil,hexamethylmelamine, hydroxyurea, ifosfamide, irinotecan, leucovorin,lomustine mechlorethamine, 6-mercaptopurine, mesna, methotrexate,mitomycin C, mitoxantrone, prednisolone, prednisone, procarbazine,raloxifen, streptozocin, tamoxifen, thioguanine, topotecan, vinblastine,vincristine, vindesine, aminoglutethimide, L-asparaginase, azathioprine,5-azacytidine cladribine, busulfan, diethylstilbestrol,2′,2′-difluorodeoxycytidine, docetaxel, erythrohydroxynonyladenine,ethynylestradiol, 5-fluorodeoxyuridine, 5-fluorodeoxyuridinemonophosphate, fludarabine phosphate, fluoxymesterone, flutamide,hydroxyprogesterone caproate, idarubicin, interferon,medroxyprogesterone acetate, megestrol acetate, melphalan, mitotane,paclitaxel, oxaliplatin, pentostatin, Nphosphonoacetyl-L-aspartate(PALA), plicamycin, semustine, teniposide, testosterone propionate,thiotepa, trimethylmelamine, uridine, vinorelbine, epothilone,gemcitabine, taxotere, BCNU, CCNU, DTIC, 5-fluorouarcil, herceptin,avastin, erbitux, sorafenib, gleevec, iressa, tarceva, rapamycin,actinomycin D, sunitinib (sutent)”.

The compounds of the present invention and/or where appropriateadditional pharmacologically active substances or pharmaceuticalcompositions as described herein can be administered in a known manner.The route of administration may thereby be any route which effectivelytransports the active compound to the appropriate or desired site ofaction, for example orally or non-orally, in particular topically,transdermally, pulmonary, rectally, intravaginally, nasally orparenteral or by implantation. Oral administration is preferred.

The compounds of the present invention and/or where appropriateadditional pharmacologically active substances or pharmaceuticalcompositions as described herein can be administered as liquid,semisolid and solid medicinal forms. This takes place in the mannersuitable in each case in the form of aerosols, powders, dusting powdersand epipastics, tablets including coated tablets, emulsions, foams,solutions, suspensions, gels, ointments, pastes, pills, pastilles,capsules or suppositories. They can be administered in a suitable dosageform to the skin, epicutaneously as solution, suspension, emulsion,foam, ointment, paste or plaster; via the oral and lingual mucosa,buccally, lingually or sublingually as tablet, pastille, coated tablet,linctus or gargle; via the gastric and intestinal mucosa, enterally astablet, coated tablet, capsule, solution, suspension or emulsion; viathe rectal mucosa, rectally as suppository, rectal capsule or ointment;via the nasal mucosa, nasally as drops, ointments or spray; via thebronchial and alveolar epithelium, by the pulmonary route or byinhalation as aerosol or inhalant; via the conjunctiva, conjunctivallyas eyedrops, eye ointment, eye tablets, lamellae or eye lotion; via themucosa of the genital organs, intravaginally as vaginal suppositories,ointments and douche, by the intrauterine route as uterine pessary; viathe urinary tract, intraurethrally as irrigation, ointment or bougie;into an artery, intraarterially as injection; into a vein, intravenouslyas injection or infusion; into the skin, intracutaneously as injectionor implant; under the skin, subcutaneously as injection or implant; intothe muscle, intramuscularly as injection or implant; into the abdominalcavity, intraperitoneally as injection or infusion.

As already explained above, the compounds of the invention can also becombined with other pharmaceutically active substances. It is possiblefor the purpose of a combination therapy to administer the individualactive ingredients simultaneously or separately, in particular either bythe same route (for example orally) or by separate routes (for exampleorally and as injection). They may be present and administered inidentical or different amounts in a unit dose. It is also possible touse a particular dosage regimen when this appears appropriate. It isalso possible in this way to combine a plurality of the novel compoundsaccording to the invention with one another.

The compounds of the invention and/or where appropriate additionalpharmacologically active substances are converted into a form which canbe administered and are mixed where appropriate with pharmaceuticallyacceptable carriers and/or auxiliaries and/or diluents. Suitableexcipients and carriers are described for example in Zanowiak P,Ullmann's Encyclopedia of Industrial Chemistry 2005, PharmaceuticalDosage Forms, 1-33; Spiegel A J et al., Journal of PharmaceuticalSciences 1963, 52: 917-927; Czetsch-Lindenwald H, Pharm. Ind. 1961, 2:72-74; Fiedler H P, Lexikon der Hilfsstoffe für Pharmazie, Kosmetik andangrenzende Gebiete 2002, Editio Cantor Verlag, p65-68.

Oral administration can take place for example in solid form as tablet,capsule, gel capsule, coated tablet, granulation or powder, but also inthe form of a drinkable solution or emulsion. The compounds of theinvention can for oral administration be combined with known andordinarily used, physiologically acceptable auxiliaries and carriers,such as, for example, gum arabic, talc, starch, sugars such as, forexample, mannitol, methylcellulose, lactose, gelatin, surface-activeagents, magnesium stearate, cyclodextrins, aqueous or nonaqueouscarriers, diluents, dispersants, emulsifiers, lubricants, preservativesand flavorings (e.g. essential oils). The compounds of the invention canalso be dispersed in a microparticulate, e.g. nanoparticulate,composition.

Non-oral administration can take place for example by intravenous,subcutaneous, intramuscular injection of sterile aqueous or oilysolutions, suspensions or emulsions, by means of implants or byointments, creams or suppositories. Administration as sustained releaseform is also possible where appropriate. Implants may comprise inertmaterials, e.g. biodegradable polymers or synthetic silicones such as,for example, silicone rubber. Intravaginal administration is possiblefor example by means of vaginal rings. Intrauterine administration ispossible for example by means of diaphragms or other suitableintrauterine devices. Transdermal administration is additionallyprovided, in particular by means of a formulation suitable for thispurpose and/or suitable means such as, for example, patches.

The dosage may vary within a wide range depending on type and/orseverity of the disease, physiological and/or pathological condition,the mode of administration, the age, gender, bodyweight and sensitivityof the subject to be treated. It is within the ability of a skilledworker to determine a “pharmacologically effective amount” of a compoundof the invention and/or additional pharmacologically active substance.Administration can take place in a single dose or a plurality ofseparate dosages.

A suitable unit dose is, for example, from 0.001 mg to 100 mg of theactive ingredient, i.e. at least one compound of the invention and,where appropriate, at least one additional pharmacologically activesubstance, per kg of a patient's bodyweight.

In another aspect, the present invention relates to a pharmaceuticalcomposition comprising a pharmacologically active amount of at least onecompound of the invention, preferably a compound of the inventionselected from the group consisting of: compound 1, 2, 3, 4, 5, 6, 7, B,9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26,27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44,45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62,63, 64, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, B0, B1, B2,B3, B5, B6, B7, B8, B9, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100,101, 102, 103, 104, 105, 106, 107, 108, 109, 110, 111, 112, 113, 114,115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128,129, 130, 131, 132, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142,143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 154, 155, 156,157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170,171, 172, 173, 174, 175, 176, 177, 178, 179, 180, 181, 182, 183, 184,185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198,199, 200, 201, 202, 203, 204, 205, 206, 207, 208, 209, 210, 211, 212,213, 214, 215, 216, 217, 218, 219, 220, 221, 222, 223, 224, 225, 226,227, 228, 229, 230, 231, 232, 233, 234, 235, 236, 237, 238, 239, 240,241, 242, 243, 244, 245, 246, 247, 248, 249, 250, 251, 252, 253, 254,255, 256, 257, 258, 259, 260, 261, 262, 263, 264, 265, 266, 267, 268,269, 270, 271, 272, 273, 274, 275, 276, 277, 278, 279, 280, 281, 282,283, 284, 285, 286, 287, 288, 289, 290, 291, 292, 293, 294, 295, 296,297, 298, 299, 300, 301, 302, 303, 304, 305, 306, 307, 308, 309, 310,311, 312, 313, 314, 315, 316, 317, 318, 319, 320, 321, 322, 323, 324,325, 326, 327, 328, 329, 330, 331, 332, 333, 334, 335, 336, 337, 338,339, 340, 341, 342, 343, 344, 345, 346, 347, 348, 349, 350, 351, 352,353, 354, 355, 356, 357, 358, 359, 360, 361, 362, 363, 364, 365, 366,367, 368, 369, 370, 371, 372, 373, 374, 375, 376, 377, 378, 379, 380,381, 382, 383, 384, 385, 386, 387, 388, 389, 390, 391, 392, 393, 394,395, 396, 397, 398, 399, 400, 401, 402, 403, 404, 405, 406, 407, 408,409, 410, 411, 412, 413, 414, 415, 416, 417, 418, 419, 420, 421, 422,423, 424, 425, 426, 427, 428, 429, 430, 431, 432, 433, 434, 435, 436,437, 438, 439, 440, 441, 442, 443, 444, 445, 446, 447, 448, 449, 450,451, 452, 453, 454, 455, 456, 457, 458, 459, 460, 461, 462, 463, 464,465, 466, 467, 468, 469, 470, 471, 472, 473, 474, 475, 476, 477, 478,479, 480, 481, 482, 483, 484, 485, 486, 487, 488, 489, 490, 491, 492,493, 494, 495, 496, 497, 498, 499, 500, 501, 502, 503, 504, 505, 506,507, 508, 509, 510, 511, 512, 513, 514, 515, 516, 517, 518, 519, 520,521, 522, 523, 524, 525, 526, 527, 528, 529, 530, 531, 532, 533, 534,535, 536, 537, 538, 539, 540, 541, 542, 543, 544, 545, 546, 547, 548,549, 550, 551, 552, 553, 554, 555, 556, 557, 558, 559, 560, 561, 562,563, 564, 565, 566, 567, 568, 569, 570, 571, 572, 573, 574, 575, 576,577, 578, 579, 580, 581, 582, 583, 584, 585, 586, 587, 588, 589, 590,591, 592, 593, 594, 595, 596, 597, 598, 599, 600, 601, 602, 603, 604,605, 606, 607, 608, 609, 610, 611, 612, 613, 614, 615, 616, 617, 618,619, 620, 621, 622, 623, 624, 625, 626, 627, 628, 629, 630, 631, 632,633, 634, 635, 636, 637, 638, 639, 640, 641, 642, 643, 644, 645, 646,647, 648, 649, 650, 651, 652, 653, 654, 655, 656, 657, 658, 659, 660,661, 662, 663, 664, 665, 666, 667, 668, 669, 670, 671, 672, 673, 674,675, 676, 677, 678, 679, 680, 681, 682, 683, 684, 685, 686, 687, 688,689, 690, 691, 692, 693, 694, 695, 696, 697, 698, 699, 700, 701, 702,703, 704, 705, 706, 707, 708, 709, 710, 711, 712, 713, 714, 715, 716,717, 718, 719, 720, 721, 722, 723, 724, 725, 726, 727, 728, 729, 730,731, 732, 733, 734, 735, 736, 737, 738, 739, 740, 741, 742, 743, 744,745, 746, 747, 748, 749, 750, 751, 752, 753, 754, 755, 756, 757, 758,759, 760, 761, 762, 763, 764, 765, 766, 767, 768, 769, 770, 771, 772,773 and/or compound 774.

In a further aspect, such a pharmaceutical composition additionallycomprises at least one pharmaceutically acceptable carrier and/orauxiliary and/or comprises at least one further pharmacologically activesubstance.

In a preferred embodiment, such further pharmacologically activesubstance is selected from the group consisting of: “DNA topoisomerase Iand/or II inhibitors, DNA intercalators, alkylating agents, microtubulidestabilizers, hormone and/or growth factor receptor agonists and/orantagonists, antibodies against growth factors and their receptors,kinase inhibitors, antimetabolites” and preferably is selected from thegroup consisting of: “asparaginase, bleomycin, carboplatin, carmustine,chlorambucil, cisplatin, colaspase, cyclophosphamide, cytarabine,dacarbazine, dactinomycin, daunorubicin, doxorubicin (adriamycin),epirubicin, etoposide, 5-fluorouracil, hexamethylmelamine, hydroxyurea,ifosfamide, irinotecan, leucovorin, lomustine mechlorethamine,6-mercaptopurine, mesna, methotrexate, mitomycin C, mitoxantrone,prednisolone, prednisone, procarbazine, raloxifen, streptozocin,tamoxifen, thioguanine, topotecan, vinblastine, vincristine, vindesine,aminoglutethimide, L-asparaginase, azathioprine, 5-azacytidinecladribine, busulfan, diethylstilbestrol, 2′,2′-difluorodeoxycytidine,docetaxel, erythrohydroxynonyladenine, ethynylestradiol,5-fluorodeoxyuridine, 5-fluorodeoxyuridine monophosphate, fludarabinephosphate, fluoxymesterone, flutamide, hydroxyprogesterone caproate,idarubicin, interferon, medroxyprogesterone acetate, megestrol acetate,melphalan, mitotane, paclitaxel, oxaliplatin, pentostatin,N-phosphonoacetyl-L-aspartate (PALA), plicamycin, semustine, teniposide,testosterone propionate, thiotepa, trimethylmelamine, uridine,vinorelbine, epothilone, gemcitabine, taxotere, BCNU, CCNU,DTIC₁₋₅-fluorouarcil, herceptin, avastin, erbitux, sorafenib, gleevec,iressa, tarceva, rapamycin, actinomycin D, sunitinib (sutent)”.

Concerning the pharmaceutical compositions of the invention, at leastone of the compounds of the invention is present in a pharmacologicallyeffective amount, preferably in a unit dose, e.g. the aforementionedunit dose, specifically and preferably in an administration form whichmakes oral administration possible. Furthermore, reference may be madeto that already said in connection with the possible uses andadministrations of the compounds of the invention.

In a further aspect of the present invention, the object of theinvention has surprisingly been solved by providing a kit comprising apharmacologically active amount of at least one compound of theinvention as detailed above and/or at least one pharmaceuticalcomposition as detailed above and a pharmacologically active amount ofat least one further pharmacologically active substance as definedabove.

General Synthesis Methods for the Compounds of the Invention:

The processes for preparing the substituted pyrido[2,3-b]pyrazinecompounds of the invention are illustrated below.

The compounds of the invention are obtainable according to the followingschemes (schemes 1-12) and corresponding processes known to thoseskilled in the art:

The definition of the R1 to R18 and X2, X3, X9 and X41 radicals shown inthe following schemes corresponds to the substituents defined above inconnection with the general formula (I), for example Z radicals, Rradicals, X radicals, Y radicals, etc. The individual assignment can beaccomplished in a simple manner by the person skilled in the art on thebasis of his or her average technical knowledge.

Precursors for selected examples of the compounds of the invention inwhich the substituent R6 is not to be H are, for example, obtainable bythe process in scheme 2 or a corresponding process known to thoseskilled in the art.

The precursors 5a, 5b, 6a and 6b from schemes 1 and 2 can be convertedto the compounds of the invention, for example, by the process inschemes 3 and 4 or a corresponding process known to those skilled in theart.

Selected examples of the compounds of the invention in which thesubstituents R1, R2 and/or R5 may be selected substituted aryl,heteroaryl, alkyl, alkenyl or alkynyl radicals are, for example,obtainable by the process in scheme 5 or corresponding processes knownto those skilled in the art.

Selected examples of the compounds of the invention in which thesubstituents R1, R2 and/or R5 may be selected NH2 or NX2×3-substitutedradicals are, for example, obtainable by the process in scheme 6 orcorresponding processes known to those skilled in the art.

Selected examples of the compounds of the invention in which thesubstituents R1 may be selected O—X9 or S—X41-substituted radicals are,for example, obtainable by the process in scheme 7 or correspondingprocesses known to those skilled in the art.

Precursors for selected examples of the compounds of the invention inwhich the substituents R3 and R4 are to be substituted by hydrogen are,for example, obtainable by the process in scheme 8 or a correspondingprocess known to those skilled in the art.

The precursors 36a and 36b from scheme 8 can be converted to thecompounds of the invention, for example, by the process in schemes 9-12or a corresponding process known to those skilled in the art.

The starting compounds and intermediates are either commerciallyavailable or can be prepared by procedures known per se or known tothose skilled in the art. The reactants 5-18 and 36-48 are valuableintermediates for the preparation of the compounds of the invention.

For the preparation of the starting compounds, intermediates and thecompounds of the invention, reference is made inter alia to the patentsWO 2004/104002 and WO 2004/104003, and also, for example, to thefollowing primary literature whose contents are hereby incorporated intothe disclosure of the present application:

-   1) Houben-Weyl, Methoden der Organischen Chemie, volume 4/1a, pp    343-350-   2) Houben-Weyl, Methoden der Organischen Chemie, 4th ed., volume E    7b (part 2), p. 579-   3) GB 1184848-   4) EP 0 735 025-   5) D. Catarzi, et al.; J. Med. Chem. 1996, 1330-1336-   6) J. K. Seydel, et al.; J. Med. Chem. 1994, 3016-3022-   7) Houben-Weyl, Methods of Organic Chemistry, Volume E 9c, pp.    231-235-   8) Houben-Weyl/Science of Synthesis, Volume 16, p. 1269-   9) C. L. Leese, H. N. Rydon J. Chem. Soc. 1955, 303-309;-   10) T. S. Osdene, G. M. Timmis J. Chem. Soc. 1955, 2033-2035-   11) W. He, et al. Bioorg. Med. Chem. Lett. 2003, 13, 3097-3100-   12) M. S. A. El-Gaby, et al. Indian J. Chem. Sect. B 2001, 40,    195-200-   13) M. R. Myers, et al. Bioorg. Med. Chem. Lett. 2003, 13, 3091-3096-   14)A. R. Renslo, et al. J. Amer. Chem. Soc. 1999, 121, 7459-7460-   15) C. O. Okafor, et al. J. Heterocyclic Chem. 1983, 20, 199-203-   16) C. R. Hopkins, et al. Tet. Lett. 2004, 45, B631-8633-   17) J. Yin, et al. Org. Lett. 2002, 4, 3481-3484-   18) O. A. El-Sayed, et al. Arch. Pharm. 2002, 335, 403-410-   19) C. Temple, et al. J. Med. Chem. 1992, 35, 988-993-   20) A. M. Thompson, et al. J. Med. Chem. 2000, 43, 4200-4211-   21) N. A. Dales, et al. Org. Lett. 2001, 2313-2316-   22) G. Dannhardt, et al. Arch. Pharm. 2000, 267-274-   23) G. S. Poindexter, et al. Bioorg. Med. Chem. 2004, 12, 507-521-   24) J.-M. Receveur, et al. Bioorg. Med. Chem. Lett. 2004, 14,    5075-5080-   25) G. Heinisch, et al. Arch. Pharm. 1997, 207-210-   26) K. Matsuno, et al. J. Med. Chem. 2002, 45, 4513-4523-   27) A. M. Papini, et al. J. Med. Chem. 2004, 47, 5224-5229-   28) J. Mindl, et al. Collect. Czech. Chem. Commun. 1983, 48, 900-905-   29) S. Sasaki, et al. J. Med. Chem. 2003, 46, 113-124-   30) B.-B. Zeng, et al. Bioorg. Med. Chem. Lett. 2004, 14, 5565-5568-   31) Q. Wang, et al. Synthetic Commun. 2004, 34, 255-264-   32) W. Mederski, et al. Bioorg. Med. Chem. Lett. 2003, 13,    13715-3718-   33) R. J. Brown, et al. Tetrahedron 2004, 60, 4361-4375-   34) L. Mao, et al. Synthesis 2004, 15, 2535-2539-   35) M. Darabantu, et al. Tetrahedron 2005, 61, 2897-2905-   36) E. Ford, et al. Tet. Lett. 2000, 41, 3197-3198-   37) T. Shiota, et al. J. Org. Chem. 1999, 64, 453-457-   38) E. C. Taylor, et al. Synthetic Commun. 1987, 17, 1865-1868-   39) G. A. Molander, et al. J. Org. Chem. 2002, 67, B424-8429-   40) G. Hughes, et al. Org. & Biomolecular Chem. 2004, 2, 3363-3367-   41) R. P. Tangallapally, et al. J. Med. Chem. 2004, 47, 5276-5283-   42) R. H. Bradburry, et al. J. Med. Chem. 1997, 40, 996-1004-   43) X. He, et al. Bioorg. Med. Chem. 2004, 12, 4003-4008-   44) A. Gopalsamy, et al. Bioorg. Med. Chem. Lett. 2005, 15,    1591-1594-   45) J.-F. Cheng, et al. Bioorg. Med. Chem. Lett. 2004, 14, 2411-2416-   46) E. R. Parmee, et al. Bioorg. Med. Chem. Lett. 2004, 14, 43-46-   47) G. Yang, et al. Synthetic Commun. 2006, 36, 5611-5619-   48) H. B. Woo, et al. Bioorg. Med. Chem. Lett. 2005, 15, 3782-3786-   49) J. F. Miravet, et al. Org. Lett. 2005, 7, 4791-4794-   50)A. L. Castelhano, et al. Bioorg. Med. Chem. Lett. 2005, 15,    1501-1504-   51) Y. Lu, et al. Bioorg. Med. Chem. Lett. 2006, 16, 915-919-   52) J. W. Szewczyk, et al. Bioorg. Med. Chem. Lett. 2006, 16,    3055-3060-   53) J. Li, et al. Bioorg. Med. Chem. Lett. 2006, 14, 2209-2224-   54) J. E. Dowling, et al. Bioorg. Med. Chem. Lett. 2005, 16,    4809-4813.

Under some of the reaction conditions specified, OH, SH and NH₂ groupsmay possibly enter into undesired side reactions. It is thereforepreferred to provide them with protecting groups or, in the case of NH₂,to replace it with NO₂, and then to eliminate the protecting group or toreduce the NO₂ group. For instance, in a modification of theabove-described processes, at least one OH group in the startingcompounds can be replaced, for example, by a benzyloxy group, and/or atleast one SH group can be replaced, for example, by an S-benzyl groupand/or at least one NH₂ group can be replaced, for example, by anNH-benzyl group or by an NO₂ group. Subsequently, at leastone—preferably all—benzyloxy group(s) or NH-benzyl group(s) can beeliminated, for example, with hydrogen and palladium on carbon, and/orat least one—preferably all—S-benzyl group(s) can be eliminated, forexample, with sodium in ammonia, and/or at least one—preferably all —NO₂group(s) can be reduced, for example, with hydrogen and Raney nickel toNH₂.

Under some of the reaction conditions mentioned, OH, NH₂ and COOH groupsmay possibly enter into undesired side reactions. It is thereforepreferred to convert starting compounds and intermediates which containat least one OH group and/or at least one NH₂ group and/or at least oneCOOH group to corresponding carboxylic ester and carboxamidederivatives. In a modification of the above-described processes,starting compounds and intermediates which have at least one OH groupand/or which have at least one NH₂ group can be converted to carboxylicester or carboxamide derivatives by reaction with an activatedcarboxylic acid group, for example a carbonyl chloride group. In amodification of the above-described processes, starting compounds andintermediates which contain at least one COOH can be converted tocarboxylic ester or carboxamide derivatives by reaction with anactivating agent, for example thionyl chloride or carbonyldiimidazole,and subsequent reaction with a suitable alcohol or amine. Subsequently,at least one—preferably all—carboxylic ester or carboxamide group(s) inthe starting compounds and intermediates can be detached, for example,with dilute aqueous acids or bases, in order to release one—preferablyall —OH group(s) and/or NH₂ group(s) and/or COOH group(s).

The compounds of the invention were named using the AutoNom 2000software (ISIS™/Draw 2.5; MDL).

The contents of all cited references are hereby incorporated byreference in their entirety. The invention is explained in more detailby means of the following examples without, however, being restrictedthereto.

EXAMPLES I) Preparation and Physicochemical Characterization of SelectedCompounds of the Invention

The general synthesis methods which are based on the synthesis schemes1-12 were used to synthesize the following compounds of the invention.In addition, their NMR spectroscopy data and mass spectrometry data andmelting points are included, respectively.

The precursors used for the preparation of the compounds of theinvention can—unless stated otherwise—be synthesized by processes knownto those skilled in the art.

The chemicals and solvents used were obtained commercially from theconventional suppliers (Acros, Aldrich, Fluka, Lancaster, Maybridge,Merck, Sigma, TCl, etc.) or synthesized.

Example 1 1-(6-Chloro-pyrido[2,3-b]pyrazin-3-yl)-3-ethyl-urea

A total of 5.0 g 6-Chloro-pyrido[2,3-b]pyrazin-3-ylamine (27.7 mmol; 1eq) was suspended in 150 mL of dry 1,4-dioxane. 2.63 g (33.2 mmol; 1.2eq) ethyl isocyanate was added and the reaction mixture was stirred at100° C. for 4 hours. Additional 1.97 g (27.7 mmol; 1 eq) of ethylisocyanate were added and the resulting solution was stirred at 100° C.for further 4 hours. After cooling to room temperature, the precipitatewas filtered of and dried in vacuo to afford 6.5 g (93.3% yield) of1-(6-Chloro-pyrido[2,3-b]pyrazin-3-yl)-3-ethyl-urea.

m.p.: 240° C.

ESI-MS: found: 252.0 (M+H⁺); calculated: 251.68 g/mol

1H-NMR (DMSO-d6) δ=10.38 (s, 1H), 9.00 (s, 1H), 8.42 (m, 2H), 7.69 (d,1H), 3.30 (m, 2H), 1.15 (t, 3H) ppm

Example 2 1-(6-Chloro-pyrido[2,3-b]pyrazin-3-yl)-3-ethyl-thiourea

A total of 5.0 g 6-Chloro-pyrido[2,3-b]pyrazin-3-ylamine (27.7 mmol; 1eq) was dissolved in 150 mL of dry DMF. 1.32 g NaH (60% dispersion inmineral oil; 33.2 mmol; 1.2 eq) was added and the dark brown solutionwas stirred at room temperature for 1 hour. 2.4 g (27.7 mmol; 1 eq)ethyl isothiocyanate was then added and the resulting mixture wasstirred at room temperature for 3 h. The reaction mixture was thenpoured into 500 mL of water. The solution was neutralized with 1 N HClwhereas the product crystallizes. The brown solid was filtered of andrecrystallised from dichloromethane/diethyl ether to afford 3.6 g (48.5%yield) of 1-(6-Chloro-pyrido[2,3-b]pyrazin-3-yl)-3-ethyl-thiourea.

m.p.: 215° C.

ESI-MS: found: 268.1 (M+H⁺); calculated: 267.74 g/mol

1H-NMR (DMSO-d₆) δ=11.55 (s, 1H), 11.40 (s, 1H), 8.88 (s, 1H), 8.44 (d,1H), 7.75 (d, 1H), 3.75 (m, 2H), 1.30 (t, 3H) ppm

Example 3 4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol

To a suspension of 1.13 g 6-Chloro-pyrido[2,3-b]pyrazin-3-ylamine (5.94mmol; 1 eq) and 1.67 g2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (6.55mmol; 1.1 eq.) in ethylene glycol dimethyl ether (45 mL) under Ar, asolution of 6.29 g sodium carbonate (59.3 mmol; 10 eq.) in water (20 mL)and a suspension of 378 mg FluoroFlash catalyst (0.24 mmol; 0.04 eq.) inundecafluoro(trifluoromethyl)cyclohexane (45 mL) were added. The mixturewas heated to 75° C. for 5 hours. Additional 0.76 g (2.97 mmol; 0.5 eq)of 2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenolwere added and the resulting mixture was stirred at 75° C. for 7.5hours. After cooling to room temperature, the aqueous and organic phasewere separated from the fluorous phase and concentrated in vacuo. Theresidue was dissolved in methanol and methylene dichloride and filtered.The black solution was again concentrated in vacuo. The residue wastaken up in water and the resulting solution was neutralized with 1N HClwhereas the product crystallizes. The brown solid was filtered of,washed with water and dried in vacuo to afford 1.5 g (80.2% yield) of4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol.

ESI-MS: found: 269.0 (M+H⁺); calculated: 268.28 g/mol

1H-NMR (DMSO-d6) δ=9.47 (s, 1H), 8.29 (s, 1H), 8.15 (d, 1H), 7.91 (d,1H), 7.84 (s, 1H), 7.67 (d, 1H), 7.34 (s, 2H), 6.90 (d, 1H), 3.89 (s,3H) ppm

Example 4 Compound1—1-Ethyl-3-(6-p-tolylamino-pyrido[2,3-b]pyrazin-3-yl)-urea

A total of 100 mg1-(6-Chloro-pyrido[2,3-b]pyrazin-3-yl)-3-ethyl-urea/example 1 (0.40mmol; 1 eq) was suspended in 3 ml of n-propanole. To this suspension 51mg p-toluidine (0.48 mmol; 1.2 eq) was added and the reaction mixturewas stirred at 100° C. for 5 hours. After cooling to room temperature,the precipitate formed was filtered and washed with diethyl ether. Thebrown crystals were dissolved in dichloromethane, washed with 0.5 N HCland NaHCO₃. The solution was dried over MgSO₄ and the solvent wasremoved to afford 74 mg (52.4% yield) of1-Ethyl-3-(6-p-tolylamino-pyrido[2,3-b]pyrazin-3-yl)-urea (compound 1)as yellow powder.

m.p.: 235° C.

ESI-MS: found: 323.0 (M+H⁺); calculated: 322.37 g/mol

1H-NMR (DMSO-d6) δ=9.97 (s, 1H), 9.14 (s, 1H), 8.72 (s, 1H), 8.23 (s,1H), 8.00 (d, 1H), 7.86 (d, 2H), 7.16 (d, 2H), 7.09 (d, 1H), 3.27 (m,2H), 1.18 (t, 3H) ppm

Example 5 Compound2—1-[6-(4-Amino-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

To a suspension of 100 mg1-(6-Chloro-pyrido[2,3-b]pyrazin-3-yl)-3-ethyl-urea/example 1 (0.39mmol; 1 eq) and 108 mg2-Methoxy-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenylamine(0.43 mmol; 1.1 eq.) in ethylene glycol dimethyl ether (4 mL) under Ar,a solution of 414 mg sodium carbonate (3.9 mmol; 10 eq.) in water (1.5mL) and a suspension of 12 mg FluoroFlash catalyst (0.01 mmol; 0.02 eq.)in undecafluoro(trifluoromethyl)cyclohexane (4 mL) were added. Themixture was heated to 60° C. for 4 hours. After cooling to roomtemperature, the aqueous and organic phase were separated from thefluorous phase and concentrated in vacuo. The residue was dissolved inmethanol and methylene dichloride and filtered. The black solution wasagain concentrated in vacuo. The residue was taken up in water and theresulting solution was neutralized with 1 N HCl whereas the productcrystallizes. The brown solid was filtered of, washed with water anddried in vacuo to afford 120 mg (86.4% yield) of1-[6-(4-Amino-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea(compound 2).

m.p.: >310° C.

ESI-MS: found: 339.1 (M+H⁺); calculated: 338.37 g/mol

1H-NMR (DMSO-d6) δ=10.15 (s, 1H), 8.88 (s, 1H), 8.55 (s, 1H), 8.26 (d,1H), 8.13 (d, 1H), 7.78 (s, 1H), 7.71 (d, 1H), 6.75 (s, 1H), 5.38 (d,2H), 3.91 (s, 3H), 3.27 (m, 2H), 1.18 (t, 3H) ppm

Example 6 Compound3—1-[6-(4-Hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-phenyl-urea

In dry 1,4-dioxane (6 mL) was stirred 111.3 mg4-(3-Amino-pyrido[2,3-b]pyrazin-6-yl)-2-methoxy-phenol/example 3 (0.35mmol; 1 eq.). The mixture was heated to 70° C. 120 mg (0.99 mmol; 2.8eq) Phenyl isocyanate was added and the reaction mixture was stirred at70° C. for 4 hours. Additional 64 mg (0.53 mmol; 1.5 eq) of Phenylisocyanate were added and the resulting mixture was stirred at 70° C.for 4 hours. After cooling to room temperature, the mixture wasconcentrated in vacuo and the residue was stirred in ethanol. Diethylether was added and the product was collected by filtration. The solidwas washed with ethanol, methylene dichloride and diethyl ether anddried in vacuo to afford 92.5 mg (67.7% yield) of1-[6-(4-Hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-phenyl-urea(compound 3).

m.p.: 240° C.

ESI-MS: found: 388.3 (M+H⁺); calculated: 387.40 g/mol

1H-NMR (DMSO-d6) δ=10.98 (s, 1H), 10.45 (s, 1H), 9.62 (s, 1H), 9.07 (s,1H), 8.40 (d, 1H), 8.26 (d, 1H), 7.96 (s, 1H), 7.82 (d, 1H), 7.61 (d,2H), 7.39 (t, 2H), 7.11 (t, 1H), 6.96 (d, 1H), 3.94 (s, 3H) ppm

The following examples were synthesized according to the Compounds 1-3and the general schemes 1-12:

Example 7 Compound 4—1-Ethyl-3-(6-phenyl-pyrido[2,3-b]pyrazin-3-yl)-urea

ESI-MS: found: 294.1 (M+H⁺); calculated: 293.0 g/mol

1H-NMR (DMSO-d6) δ=10.27 (s, 1H); 8.97 (s, 1H); 8.65 (s, 1H); 8.45 (d,1H); 8.29 (dd, 2H); 8.26 (d, 1H); 7.53-7.60 (m, 3H); 3.32-3.36 (m, 2H);1.20 (t, 3H) ppm.

Example 8 Compound5—1-Ethyl-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

ESI-MS: found: 340.2 (M+H⁺); calculated: 339.0 g/mol

1H-NMR (DMSO-d6) δ=10.21 (s, 1H); 9.58 (s, 1H); 8.94 (s, 1H); 8.55 (s,1H); 8.35 (d, 1H); 8.20 (dd, 1H); 7.89 (d, 1H); 7.78 (dd, 1H); 6.94 (d,1H); 3.92 (s, 3H); 3.29-3.35 (m, 2H); 1.19 (t, 3H) ppm.

Example 9 Compound6—1-[6-(4-Chloro-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

m.p.: 276° C.

ESI-MS: found: 328.2 (M+H⁺); calculated: 327.0 g/mol

1H-NMR (DMSO-d6) δ=10.29 (s, 1H); 8.97 (s, 1H); 8.65 (s, 1H); 8.45 (d,1H); 8.33 (dd, 1H); 8.27 (d, 1H); 7.64 (d, 2H); 3.31-3.35 (m, 2H); 1.19(t, 3H) ppm.

Example 10 Compound7—1-Ethyl-3-(6-pyridin-4-yl-pyrido[2,3-b]pyrazin-3-yl)-urea

m.p.: 211° C.

ESI-MS: found: 295.2 (M+H⁺); calculated: 294.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.35 (s, 1H); 9.03 (s, 1H); 8.80 (d, 2H); 8.62 (s,1H); 8.54 (d, 1H); 8.36 (d, 1H); 8.23 (d, 2H); 3.31-3.36 (m, 2H); 1.20(t, 3H) ppm.

Example 11 Compound8—1-[6-(3-Chloro-4-hydroxy-5-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

ESI-MS: found: 374.3 (M+H⁺); calculated: 373.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.23 (s, 1H); 10.00 (s, 1H); 8.97 (s, 1H); 8.53 (s,1H); 8.38 (d, 1H); 8.28 (d, 1H); 7.94 (d, 1H); 7.87 (d, 1H); 3.98 (s,3H); 3.31-3.35 (m, 2H); 1.19 (t, 3H) ppm.

Example 12 Compound9—1-[6-(3,5-Dichloro-4-hydroxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

m.p.: >300° C.

ESI-MS: found: 378.4 (M+H⁺); calculated: 377.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.00 (s, 1H); 8.71 (s, 1H); 8.66 (s, 1H); 8.05 (d,1H); 8.00 (s, 2H); 7.92 (d, 1H); 3.31-3.35 (m, 2H); 1.18 (t, 3H) ppm.

Example 13 Compound10—1-Ethyl-3-[6-(1-methyl-1H-pyrazol-4-yl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 211° C.

ESI-MS: found: 298.2 (M+H⁺); calculated: 297.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.17 (s, 1H); 8.85 (s, 1H); 8.65 (s, 1H); 8.51 (s,1H); 8.29 (d, 1H); 8.19 (s, 1H); 7.91 (d, 1H); 3.94 (s, 3H); 3.31-3.35(m, 2H); 1.19 (t, 3H) ppm.

Example 14 Compound11—1-Ethyl-3-[6-(4-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 244° C.

ESI-MS: found: 323.9 (M+H⁺); calculated: 323.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.22 (s, 1H); 8.92 (s, 1H); 8.65 (s, 1H); 8.38 (d,1H); 8.27 (d, 2H); 8.20 (d, 1H); 7.12 (d, 2H); 3.86 (s, 3H); 3.31-3.36(m, 2H); 1.19 (t, 3H) ppm.

Example 15 Compound12—1-Ethyl-3-[6-(3-isopropoxy-phenylamino)-pyrido[2,3-b]pyrazin-3-yl]-urea

ESI-MS: found: 367.0 (M+H⁺); calculated: 366.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.02 (s, 1H); 9.77 (s, 1H); 8.67 (s, 1H); 8.47 (s,1H); 8.03 (d, 1H); 7.97 (s, 1H); 7.20-7.22 (m, 2H); 7.11 (d, 1H);6.57-6.60 (m, 1H); 4.57-4.63 (m, 1H); 3.26-3.31 (m, 2H); 1.30 (d, 6H);1.19 (t, 3H) ppm.

Example 16 Compound13—1-Ethyl-3-(6-phenylamino-pyrido[2,3-b]pyrazin-3-yl)urea

m.p.: 202° C.

ESI-MS: found: 309.1 (M+H⁺); calculated: 308.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.00 (s, 1H); 9.81 (s, 1H); 8.74 (s, 1H); 8.22 (s,1H); 8.03 (d, 1H); 7.98 (d, 2H); 7.35 (dd, 2H); 7.13 (d, 1H); 7.02 (dd,1H); 3.24-3.30 (m, 2H); 1.18 (t, 31-I) ppm.

Example 17 Compound14—1-Phenyl-3-(6-phenylamino-pyrido[2,3-b]pyrazin-3-yl)-urea

m.p.: 251° C.

ESI-MS: found: 357.3 (M+H⁺); calculated: 356.0 g/mol

¹H-NMR (DMSO-d₆) δ=11.13 (s, 1H); 10.31 (s, 1H); 9.90 (s, 1H); 8.75 (s,1H); 8.08 (d, 1H); 8.06 (d, 2); 7.59 (d, 2H); 7.37-7.42 (m, 4H); 7.18(d, 1H); 7.09 (dd, 1H); 7.06 (dd, 1H) ppm.

Example 18 Compound15—1-[6-(3,5-Dichloro-4-hydroxy-phenylamino)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

m.p.: 272° C.

ESI-MS: found: 393.3 (M+H⁺); calculated: 392.0 g/mol

¹H-NMR (DMSO-d₆) δ=10.06 (s, 1H); 9.85 (s, 1H); 9.72 (s, 1H); 8.69 (s,1H); 8.42 (s, 1H); 8.09 (s, 2H); 8.04 (d, 1H); 7.04 (d, 1H); 3.25-3.30(m, 2H); 1.22 (t, 3H) ppm.

Example 19 Compound16—1-[6-(4-Hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-propyl-urea

m.p.: 220-222° C.

ESI-MS: found: 354.1 (M+H⁺); calculated: 353.38 g/mol

¹H-NMR (DMSO-d₆) δ=10.25 (s, 1H), 9.59 (s, 1H), 8.90 (bs, 1H), 8.87 (s,1H), 8.34 (d, 1H), 8.20 (d, 1H), 7.92 (s, 1H), 7.77 (d, 1H), 6.94 (d,1H), 3.91 (s, 3H), 3.27-3.33 (m, 2H), 1.60 (m, 2H), 1.04 (t, 3H) ppm

Example 20 Compound17—1-Cyclohexyl-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 232-235° C.

ESI-MS: found: 394.2 (M+H⁺); calculated: 393.44 g/mol

¹H-NMR (DMSO-d₆) δ=10.19 (s, 1H), 9.60 (s, 1H), 9.10 (bs, 1H), 8.85 (s,1H), 8.34 (d, 1H), 8.21 (d, 1H), 7.94 (s, 1H), 7.77 (d, 1H), 6.94 (d,1H), 3.91 (s, 3H), 3.78 (m, 1H), 1.75-1.85 (m, 4H), 1.40-1.54 (m, 6H)ppm

Example 21 Compound18—1-Allyl-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 211-213° C.

ESI-MS: found: 352.0 (M+H⁺); calculated: 351.36 g/mol

¹H-NMR (DMSO-d₆) δ=10.33 (s, 1H), 9.59 (s, 1H), 8.94 (bs, 1H), 8.90 (bs,1H), 8.35 (d, 1H), 8.21 (d, 1H), 7.89 (s, 1H), 7.77 (d, 1H), 6.94 (d,1H), 6.00 (m, 1H), 5.38 (d, 1H), 5.19 (d, 1H), 3.97 (t, 2H), 3.91 (s,3H) ppm

Example 22 Compound19—1-[6-(4-Hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-isopropyl-urea

m.p.: 212-214° C.

ESI-MS: found: 354.0 (M+H⁺); calculated: 353.38 g/mol

¹H-NMR (DMSO-d₆) δ=10.10 (s, 1H), 9.59 (s, 1H), 8.94 (s, 1H), 8.58 (bs,1H), 8.34 (d, 1H), 8.21 (d, 1H), 7.92 (s, 1H), 7.77 (d, 1H), 6.94 (d,1H), 3.92 (m, 1H), 3.91 (s, 3H), 1.24 (d, 6H) ppm

Example 23 Compound20—1-Cyclopentyl-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 222-225° C.

ESI-MS: found: 380.1 (M+H⁺); calculated: 379.42 g/mol

¹H-NMR (DMSO-d₆) δ=10.15 (s, 1H), 9.60 (s, 1H), 9.09 (bs, 1H), 8.85 (s,1H), 8.34 (d, 1H), 8.20 (d, 1H), 7.96 (s, 1H), 7.77 (d, 1H), 6.94 (d,1H), 4.15 (m, 1H), 3.91 (s, 3H), 1.92 (m, 2H), 1.81 (m, 2H), 1.66 (m,2H), 1.57 (m, 2H) ppm

Example 24 Compound21—1-Ethyl-3-[6-(4-hydroxy-3-methoxy-phenylamino)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 255° C.

ESI-MS: found: 355.0 (M+H⁺); calculated: 354.37 g/mol

¹H-NMR (DMSO-d₆) δ=9.94 (bs, 1H), 9.59 (s, 1H), 8.68 (bs, 2H), 8.55 (s,1H), 7.95 (d, 1H), 7.83 (s, 1H), 7.19 (d, 1H), 7.04 (d, 1H), 6.75 (d,1H), 3.82 (s, 3H), 3.27 (m, 2H), 1.15 (t, 3H) ppm

Example 25 Compound22—1-[6-(3,4-Dimethoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

m.p.: >235° C.

ESI-MS: found: 354.1 (M+H⁺); calculated: 353.38 g/mol

¹H-NMR (DMSO-d₆) δ=10.23 (s, 1H), 8.98 (s, 1H), 8.53 (bs, 1H), 8.38 (d,1H), 8.25 (d, 1H), 7.90 (s, 1H), 7.88 (d, 1H), 7.14 (d, 1H), 3.91 (s,3H), 3.86 (s, 3H), 3.32 (m, 2H), 1.19 (t, 3H) ppm

Example 26 Compound23—1-Ethyl-3-[6-(3,4,5-trimethoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: >230° C.

ESI-MS: found: 384.1 (M+H⁺); calculated: 383.41 g/mol

¹H-NMR (DMSO-d₆) δ=10.25 (s, 1H), 9.03 (s, 1H), 8.44 (bs, 1H), 8.42 (d,1H), 8.32 (d, 1H), 7.60 (s, 2H), 3.93 (s, 6H), 3.76 (s, 3H), 3.32 (m,2H), 1.19 (t, 3H) ppm

Example 27 Compound24—1-Ethyl-3-[6-(4-hydroxy-phenylamino)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 277° C.

ESI-MS: found: 325.1 (M+H⁺); calculated: 324.34 g/mol

¹H-NMR (DMSO-d₆) δ=9.92 (s, 1H), 9.59 (s, 1H), 9.16 (bs, 1H), 8.65 (s,1H), 8.34 (bs, 1H), 7.94 (d, 1H), 7.70 (d, 2H), 7.04 (d, 1H), 6.76 (d,2H), 3.26 (m, 2H), 1.16 (t, 3H) ppm

Example 28 Compound25—1-Ethyl-3-(6-p-tolylamino-pyrido[2,3-b]pyrazin-3-yl)-thiourea

m.p.: 195° C.

ESI-MS: found: 339.0 (M+H⁺); calculated: 338.44 g/mol

¹H-NMR (DMSO-d₆) δ=11.97 (t, 1H), 11.14 (s, 1H), 9.81 (s, 1H), 8.48 (s,1H), 8.02 (d, 1H), 7.87 (d, 2H), 7.13-7.15 (d, 3H), 3.67 (m, 2H), 2.29(s, 3H), 1.36 (t, 3H) ppm

Example 29 Compound26—1-[6-(4-Hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-phenethyl-urea

m.p.: 235-237° C.

ESI-MS: found: 416.2 (M+H⁺); calculated: 415.46 g/mol

1H-NMR (DMSO-d6) δ=10.26 (s, 1H), 9.59 (s, 1H), 8.89 (s, 1H), 8.74 (s,1H), 8.35 (d, 1H), 8.22 (d, 1H), 7.93 (s, 1H), 7.80 (d, 1H), 7.44 (d,2H), 7.27 (t, 2H), 7.18 (t, 1H), 6.95 (d, 1H), 3.88 (s, 3H), 3.53 (m,2H), 2.92 (t, 2H) ppm

Example 30 Compound27—1-(3,5-Dimethyl-isoxazol-4-yl)-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 249-252° C.

ESI-MS: found: 407.2 (M+H⁺); calculated: 406.40 g/mol

1H-NMR (DMSO-d6) δ=10.64 (s, 1H), 10.10 (s, 1H), 9.61 (s, 1H), 9.01 (s,1H), 8.40 (d, 1H), 8.26 (d, 1H), 7.90 (s, 1H), 7.79 (d, 1H), 6.94 (d,1H), 3.91 (s, 3H), 2.40 (s, 3H), 2.25 (s, 3H) ppm

Example 31 Compound28—1-tert-Butyl-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 219-222° C.

ESI-MS: found: 368.1 (M+H⁺); calculated: 367.41 g/mol.

1H-NMR (DMSO-d6) δ=10.01 (s, 1H), 9.58 (s, 1H), 8.96 (s, 1H), 8.86 (s,1H), 8.33 (d, 1H), 8.20 (d, 1H), 7.94 (s, 1H), 7.77 (d, 1H), 6.93 (d,1H), 3.90 (s, 3H), 1.43 (s, 9H) ppm

Example 32 Compound29—1-Benzyl-3-[6-(4-hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 229-231° C.

ESI-MS: found: 402.2 (M+H⁺); calculated: 401.43 g/mol

1H-NMR (DMSO-d6) δ=10.36 (s, 1H), 9.58 (s, 1H), 9.11 (s, 1H), 8.94 (s,1H), 8.35 (d, 1H), 8.20 (d, 1H), 7.85 (s, 1H), 7.75 (d, 1H), 7.43 (d,2H), 7.38 (t, 2H), 7.29 (t, 1H), 6.93 (d, 1H), 4.54 (d, 2H), 3.88 (s,3H) ppm

Example 33 Compound30—1-[6-(4-Hydroxy-3-methoxy-phenyl)-pyrido[2,3-b]pyrazin-3-yl]-3-[1-(2,2,2-trifluoro-acetyl)-piperidin-4-yl]-urea

m.p.: 236-239° C.

ESI-MS: found: 491.2 (M+H⁺); calculated: 490.45 g/mol

1H-NMR (DMSO-d6) δ=10.29 (s, 1H), 9.60 (s, 1H), 9.19 (s, 1H), 8.89 (s,1H), 8.35 (d, 1H), 8.22 (d, 1H), 7.92 (s, 1H), 7.76 (d, 1H), 6.92 (d,1H), 4.04 (m, 2H), 3.88 (s, 3H), 3.83 (m, 1H), 3.57 (m, 1H), 3.48 (m,1H), 2.06 (m, 2H), 1.63 (m, 2H) ppm

Example 34 Compound31—1-[6-(3-Chloro-4-hydroxy-phenylamino)-pyrido[2,3-b]pyrazin-3-yl]-3-ethyl-urea

m.p: 277-280° C.

ESI-MS: found: 359.1 (M+H⁺); calculated: 358.79 g/mol

1H-NMR (DMSO-d6) δ=10.00 (s, 1H), 9.78 (s, 1H), 9.71 (s, 1H), 8.65 (s,1H), 8.46 (s, 1H), 7.99 (d, 1H), 7.35 (m, 1H), 7.05 (d, 1H), 6.94 (d,1H), 3.26 (m, 2H), 1.20 (m, 3H) ppm

Example 35 Compound32—1-Ethyl-3-[6-(quinolin-3-ylamino)-pyrido[2,3-b]pyrazin-3-yl]-urea

m.p.: 265-270° C.

ESI-MS: found: 360.4 (M+H⁺); calculated: 359.39 g/mol

1H-NMR (DMSO-d6) δ=10.31 (s, 1H), 10.09 (s, 1H), 9.34 (d, 1H), 9.05 (d,1H), 8.75 (s, 1H), 8.52 (s, 1H), 8.14 (d, 1H), 7.96 (d, 1H), 7.84 (d,1H), 7.60 (m, 2H), 7.25 (d, 1H), 3.33 (m, 2H), 1.26 (m, 3H) ppm

Example 36 Compound 33

ESI-MS: found: 760.5 (M+H⁺); calculated: 759.79 g/mol

Example 37 Compound 34

m.p.: 182-184° C.

ESI-MS: found: 476.3 (M+H⁺); calculated: 475.44 g/mol

Example 38 Compound 35

m.p.: 245-247° C.

ESI-MS: found: 365.2 (M+H⁺); calculated: 364.41 g/mol

Example 39 Compound 36

m.p.: 177° C.

ESI-MS: found: 338.3 (M+H⁺); calculated: 337.38 g/mol

Example 40 Compound 37

m.p.: 247-249° C.

ESI-MS: found: 452.2 (M+H⁺); calculated: 451.89 g/mol

Example 41 Compound 38

ESI-MS: found: 368.2 (M+H⁺); calculated: 367.41 g/mol.

Example 42 Compound 39

ESI-MS: found: 402.2 (M+H⁺); calculated: 401.85 g/mol.

Example 43 Compound 40

m.p.: >240° C.

ESI-MS: found: 441.4 (M+H⁺); calculated: 440.46 g/mol.

Example 44 Compound 41

m.p.: >350° C.

ESI-MS: found: 420.3 (M+H⁺); calculated: 463.30 g/mol.

Example 45 Compound 42

m.p.: 238-241° C.

ESI-MS: found: 389.3 (M+H⁺); calculated: 388.33 g/mol.

Example 46 Compound 43

m.p.: 246-249° C.

ESI-MS: found: 418.2 (M+H⁺); calculated: 417.44 g/mol.

Example 47 Compound 44

m.p.: >330° C.

ESI-MS: found: 529.3 (M+H⁺); calculated: 528.56 g/mol.

Example 48 Compound 45

ESI-MS: found: 367.2 (M+H⁺); calculated: 366.38 g/mol.

Example 49 Compound 46

m.p.: >270° C.

ESI-MS: found: 340.3 (M+H⁺); calculated: 339.35 g/mol.

Example 50 Compound 47

m.p.: 337-339° C.

ESI-MS: found: 390.2, 388.3 (M+H⁺); calculated: 388.22 g/mol.

Example 51 Compound 48

m.p.: 276-279° C.

ESI-MS: found: 422.3 (M+H⁺); calculated: 421.46 g/mol.

Example 52 Compound 49

m.p.: 134° C.

ESI-MS: found: 379.4 (M+H⁺); calculated: 378.43 g/mol.

Example 53 Compound 50

m.p.: 195-200° C.

ESI-MS: found: 383.2 (M+H⁺); calculated: 382.38 g/mol.

Example 54 Compound 51

m.p.: 231-232° C.

ESI-MS: found: 353.1 (M+H⁺); calculated: 352.40 g/mol.

Example 55 Compound 52

m.p.: 218-220° C.

ESI-MS: found: 284.1 (M+H⁺); calculated: 283.29 g/mol.

Example 56 Compound 53

m.p.: 257-259° C.

ESI-MS: found: 298.3 (M+H⁺); calculated: 297.32 g/mol.

Example 57 Compound 54

m.p.: 227-229° C.

ESI-MS: found: 382.1 (M+H⁺); calculated: 381.39 g/mol.

Example 58 Compound 55

m.p.: 243-246° C.

ESI-MS: found: 325.2 (M+H⁺); calculated: 324.34 g/mol.

Example 59 Compound 56

m.p.: 270-273° C.

ESI-MS: found: 325.3 (M+H⁺); calculated: 324.34 g/mol.

Example 60 Compound 57

m.p.: 181-183° C.

ESI-MS: found: 400.3 (M+H⁺); calculated: 399.45 g/mol.

Example 61 Compound 58

m.p.: 258-261° C.

ESI-MS: found: 374.2 (M+H⁺); calculated: 373.42 g/mol.

Example 62 Compound 59

m.p.: 189-191° C.

ESI-MS: found: 340.3 (M+H⁺); calculated: 339.40 g/mol.

Example 63 Compound 60

m.p.: 223-226° C.

ESI-MS: found: 397.3 (M+H⁺); calculated: 396.45 g/mol.

Example 64 Compound 61

m.p.: 270-274° C.

ESI-MS: found: 334.2 (M+H⁺); calculated: 333.35 g/mol.

Example 65 Compound 62

m.p.: 179-181° C.

ESI-MS: found: 366.2 (M+H⁺); calculated: 365.43 g/mol.

Example 66 Compound 63

m.p.: 225-227° C.

ESI-MS: found: 467.3 (M+H⁺); calculated: 466.54 g/mol.

Example 67 Compound 64

m.p.: 229-231° C.

ESI-MS: found: 309.2 (M+H⁺); calculated: 308.34 g/mol.

Example 68 Compound 65

ESI-MS: found: 480.3 (M+H⁺); calculated: 479.58 g/mol.

Example 69 Compound 66

m.p.: 276-279° C.

ESI-MS: found: 351.2 (M+H⁺); calculated: 350.38 g/mol.

Example 70 Compound 67

m.p.: 200-202° C.

ESI-MS: found: 432.0 (M+H⁺); calculated: 430.30 g/mol.

Example 71 Compound 68

m.p.: 182-185° C.

ESI-MS: found: 354.1 (M+H⁺); calculated: 353.38 g/mol.

Example 73 Compound 70

m.p.: >300° C.

ESI-MS: found: 333.2 (M+H⁺); calculated: 332.37 g/mol.

Example 74 Compound 71

m.p.: >300° C.

ESI-MS: found: 384.2 (M+H⁺); calculated: 383.41 g/mol.

Example 75 Compound 72

m.p.: >300° C.

ESI-MS: found: 311.0 (M+H⁺); calculated: 310.32 g/mol.

Example 76 Compound 73

ESI-MS: found: 375.2 (M+H⁺); calculated: 374.35 g/mol.

Example 77 Compound 74

ESI-MS: found: 456.2 (M+H⁺); calculated: 455.54 g/mol.

Example 78 Compound 75

ESI-MS: found: 356.2 (M+H⁺); calculated: 355.42 g/mol.

Example 79 Compound 76

m.p.: 253° C.

ESI-MS: found: 423.2 (M+H⁺); calculated: 422.44 g/mol.

Example 80 Compound 77

m.p.: >300° C.

ESI-MS: found: 381.2 (M+H⁺); calculated: 380.41 g/mol.

Example 81 Compound 78

m.p.: >350° C.

ESI-MS: found: 354.2 (M+H⁺); calculated: 353.34 g/mol.

Example 82 Compound 79

m.p.: 238.1-241.8° C.

ESI-MS: found: 354.2 (M+H⁺); calculated: 353.36 g/mol.

Example 83 Compound 80

m.p.: 255.3-258.2° C.

ESI-MS: found: 351.8 (M+H⁺); calculated: 351.41 g/mol.

Example 84 Compound 81

m.p.: 305.4-307.2° C.

ESI-MS: found: 348.2 (M+H⁺); calculated: 347.30 g/mol.

Example 85 Compound 82

m.p.: 255.3-257.9° C.

ESI-MS: found: 321.8 (M+H⁺); calculated: 321.38 g/mol.

Example 86 Compound 83

m.p.: 247.8-252.4° C.

ESI-MS: found: 326.2 (M+H⁺); calculated: 325.35 g/mol.

Example 87 Compound 84

m.p.: 263.9-265.6° C.

ESI-MS: found: 388.3 (M+H⁺); calculated: 387.42 g/mol.

Example 88 Compound 85

m.p.: 253.3-256.2° C.

ESI-MS: found: 353.2 (M+H⁺); calculated: 352.35 g/mol.

Example 89 Compound 86

m.p.: 277-280° C.

ESI-MS: found: 339.3 (M+H⁺); calculated: 338.37 g/mol.

Example 90 Compound 87

m.p.: 256-259° C.

ESI-MS: found: 397.2 (M+H⁺); calculated: 396.40 g/mol.

Example 91 Compound 88

m.p.: 240-242° C.

ESI-MS: found: 306.5 (M+H⁺); calculated: 610.68 g/mol.

Example 92 Compound 89

m.p.: 216-219° C.

ESI-MS: found: 339.0 (M+H⁺); calculated: 338.37 g/mol.

Example 93 Compound 90

m.p.: 298-305° C.

ESI-MS: found: 362.3 (M+H⁺); calculated: 362.22 g/mol.

Example 94 Compound 91

m.p.: 254-257° C.

ESI-MS: found: 358.1 (M+H⁺); calculated: 357.80 g/mol.

Example 95 Compound 92

m.p.: 264-269° C.

ESI-MS: found: 362.2 (M+H⁺); calculated: 362.22 g/mol.

Example 96 Compound 93

m.p.: 253-258° C.

ESI-MS: found: 342.1 (M+H⁺); calculated: 341.34 g/mol.

Example 97 Compound 94

m.p.: 270-274° C.

ESI-MS: found: 386.2 (M+H⁺); calculated: 386.25 g/mol.

Example 98 Compound 95

m.p.: 259-262° C.

ESI-MS: found: 330.3 (M+H⁺); calculated: 329.31 g/mol.

Example 99 Compound 96

m.p.: 258-259° C.

ESI-MS: found: 360.2 (M+H⁺); calculated: 359.79 g/mol.

Example 100 Compound 97

m.p.: 240-243° C.

ESI-MS: found: 361.9 (M+H⁺); calculated: 361.33 g/mol.

Example 101 Compound 98

m.p.: 223-225° C.

ESI-MS: found: 338.0 (M+H⁺); calculated: 337.38 g/mol.

Example 102 Compound 99

m.p.: 275° C.

ESI-MS: found: 346.2 (M+H⁺); calculated: 345.76 g/mol.

Example 103 Compound 100

m.p.: 232-234° C.

ESI-MS: found: 307.9 (M+H⁺); calculated: 307.36 g/mol.

Example 104 Compound 101

m.p.: 249-253° C.

ESI-MS: found: 339.1 (M+H⁺); calculated: 338.33 g/mol.

Example 105 Compound 102

m.p.: 220-222° C.

ESI-MS: found: 337.8 (M+H⁺); calculated: 337.38 g/mol.

Example 106 Compound 103

m.p.: 226-228° C.

ESI-MS: found: 311.8 (M+H⁺); calculated: 311.32 g/mol.

Example 107 Compound 104

m.p.: 310° C.

ESI-MS: found: 328.2 (M+H⁺); calculated: 327.77 g/mol.

Example 108 Compound 105

m.p.: 218-220° C.

ESI-MS: found: 307.9 (M+H⁺); calculated: 307.36 g/mol.

Example 109 Compound 106

m.p.: 270° C.

ESI-MS: found: 326.0 (M+H⁺); calculated: 325.35 g/mol.

Example 110 Compound 107

m.p.: 260° C.

ESI-MS: found: 321.9 (M+H⁺); calculated: 321.38 g/mol.

Example 111 Compound 108

m.p.: >350° C.

ESI-MS: found: 362.2 (M+H⁺); calculated: 362.22 g/mol.

Example 112 Compound 109

m.p.: 236-238° C.

ESI-MS: found: 494.0, 492.0 (M+H⁺); calculated: 492.37 g/mol.

Example 113 Compound 110

m.p.: 228-230° C.

ESI-MS: found: 417.9, 416.1 (M+H⁺); calculated: 416.28 g/mol.

Example 114 Compound 111

m.p.: 262-264° C.

ESI-MS: found: 328.1 (M+H⁺); calculated: 327.77 g/mol.

Example 115 Compound 112

m.p.: 229-231° C.

ESI-MS: found: 356.1 (M+H⁺); calculated: 355.37 g/mol.

Example 116 Compound 113

m.p.: 242° C.

ESI-MS: found: 314.2 (M+H⁺); calculated: 313.39 g/mol.

Example 117 Compound 114

m.p.: 253-257° C.

ESI-MS: found: 318.9 (M+H⁺); calculated: 318.34 g/mol.

Example 118 Compound 115

m.p.: 200-202° C.

ESI-MS: found: 323.9 (M+H⁺); calculated: 323.35 g/mol.

Example 119 Compound 116

m.p.: 251-255° C.

ESI-MS: found: 370.3 (M+H⁺); calculated: 369.43 g/mol.

Example 120 Compound 117

m.p.: 221-224° C.

ESI-MS: found: 340.0 (M+H⁺); calculated: 339.42 g/mol.

Example 121 Compound 118

m.p.: 239-240° C.

ESI-MS: found: 378.1 (M+H⁺); calculated: 377.32 g/mol.

Example 122 Compound 119

m.p.: 222-223° C.

ESI-MS: found: 366.0 (M+H⁺); calculated: 365.39 g/mol.

Example 123 Compound 120

m.p.: 224-228° C.

ESI-MS: found: 387.1 (M+H⁺); calculated: 386.43 g/mol.

Example 124 Compound 121

m.p.: 212-217° C.

ESI-MS: found: 460.1 (M+H⁺); calculated: 459.50 g/mol.

Example 125 Compound 122

m.p.: 244-247° C.

ESI-MS: found: 328.0 (M+H⁺); calculated: 327.77 g/mol.

Example 126 Compound 123

m.p.: 280° C.

ESI-MS: found: 370.2 (M+H⁺); calculated: 369.43 g/mol.

Example 127 Compound 124

m.p.: 246° C.

ESI-MS: found: 324.0 (M+H⁺); calculated: 323.42 g/mol.

Example 128 Compound 125

m.p.: 244° C.

ESI-MS: found: 354.2 (M+H⁺); calculated: 353.45 g/mol.

Example 129 Compound 126

m.p.: 278° C.

ESI-MS: found: 339.1 (M+H⁺); calculated: 338.44 g/mol.

Example 130 Compound 127

m.p.: 227° C.

ESI-MS: found: 368.0 (M+H⁺); calculated: 367.47 g/mol.

Example 131 Compound 128

m.p.: 269-273° C.

ESI-MS: found: 461.4 (M+H⁺); calculated: 460.54 g/mol.

Example 132 Compound 129

m.p.: 283-286° C.

ESI-MS: found: 311.9 (M+H⁺); calculated: 311.32 g/mol.

Example 133 Compound 130

m.p.: 220-223° C.

ESI-MS: found: 337.8 (M+H⁺); calculated: 337.38 g/mol.

Example 134 Compound 131

m.p.: >350° C.

ESI-MS: found: 339.1 (M+H⁺); calculated: 338.33 g/mol.

Example 135 Compound 132

m.p.: 260° C.

ESI-MS: found: 351.9 (M+H⁺); calculated: 351.36 g/mol.

Example 136 Compound 133

m.p.: 258.7° C.

ESI-MS: found: 351.8 (M+H⁺); calculated: 351.41 g/mol.

Example 137 Compound 134

m.p.: 230° C.

ESI-MS: found: 400.3 (M+H⁺); calculated: 399.47 g/mol.

Example 138 Compound 135

m.p.: 182-185° C.

ESI-MS: found: 340.0 (M+H⁺); calculated: 339.42 g/mol.

Example 139 Compound 136

m.p.: 256-260° C.

ESI-MS: found: 319.1 (M+Fr); calculated: 318.34 g/mol.

Example 140 Compound 137

m.p.: 236-239° C.

ESI-MS: found: 342.0 (M+H⁺); calculated: 341.34 g/mol.

Example 141 Compound 138

ESI-MS: found: 394.4 (M+H⁺); calculated: 394.28 g/mol.

Example 142 Compound 139

ESI-MS: found: 390.3 (M+H⁺); calculated: 389.87 g/mol.

Example 143 Compound 140

ESI-MS: found: 355.3 (M+H⁺); calculated: 354.44 g/mol.

Example 144 Compound 141

m.p.: 250° C.

ESI-MS: found: 299.9 (M+H⁺); calculated: 299.36 g/mol.

Example 145 Compound 142

m.p.: 247-249° C.

ESI-MS: found: 321.9 (M+H⁺); calculated: 321.38 g/mol.

Example 146 Compound 143

m.p.: 250-252° C.

ESI-MS: found: 370.2 (M+H⁺); calculated: 369.35 g/mol.

Example 147 Compound 144

m.p.: 240-244° C.

ESI-MS: found: 336.9 (M+H⁺); calculated: 336.40 g/mol.

Example 148 Compound 145

m.p.: 207-209° C.

ESI-MS: found: 353.9 (M+H⁺); calculated: 353.38 g/mol.

Example 149 Compound 146

m.p.: 202-204° C.

ESI-MS: found: 356.0 (M+H⁺); calculated: 355.37 g/mol.

Example 150 Compound 147

m.p.: 272° C.

ESI-MS: found: 371.3 (M+H⁺); calculated: 370.44 g/mol.

Example 151 Compound 148

m.p.: 285° C.

ESI-MS: found: 325.1 (M+H⁺); calculated: 324.41 g/mol.

Example 152 Compound 149

m.p.: 280° C.

ESI-MS: found: 341.2 (M+H⁺); calculated: 340.41 g/mol.

Example 153 Compound 150

m.p.: 269° C.

ESI-MS: found: 371.1 (M+H⁺); calculated: 370.44 g/mol.

Example 154 Compound 151

m.p.: 228-233° C.

ESI-MS: found: 335.7 (M+H⁺); calculated: 335.41 g/mol.

Example 155 Compound 152

m.p.: 227-228° C.

ESI-MS: found: 300.0 (M+H⁺); calculated: 299.36 g/mol.

Example 156 Compound 153

m.p.: 225° C.

ESI-MS: found: 339.0 (M+H⁺); calculated: 338.37 g/mol.

Example 157 Compound 154

m.p.: 238° C.

ESI-MS: found: 339.0 (M+H⁺); calculated: 338.37 g/mol.

Example 158 Compound 155

m.p.: 230° C.

ESI-MS: found: 401.0 (M+H⁺); calculated: 400.44 g/mol.

Example 159 Compound 156

m.p.: 281° C.

ESI-MS: found: 355.1 (M+H⁺); calculated: 354.37 g/mol.

Example 160 Compound 157

m.p.: 265° C.

ESI-MS: found: 385.1 (M+H⁺); calculated: 384.46 g/mol.

Example 161 Compound 158

ESI-MS: found: 375.1 (M+H⁺); calculated: 374.85 g/mol.

Example 162 Compound 159

m.p.: 276° C.

ESI-MS: found: 389.1 (M+H⁺); calculated: 388.88 g/mol.

Example 163 Compound 160

m.p.: 268° C.

ESI-MS: found: 415.1 (M+H⁺); calculated: 414.49 g/mol.

Example 164 Compound 161

m.p.: 262° C.

ESI-MS: found: 341.1 (M+H⁺); calculated: 340.41 g/mol.

Example 165 Compound 162

m.p.: 288° C.

ESI-MS: found: 369.1 (M+H⁺); calculated: 368.46 g/mol.

Example 166 Compound 163

m.p.: 238° C.

ESI-MS: found: 383.1 (M+H⁺); calculated: 382.49 g/mol.

Example 167

Compound 164

m.p.: 294° C.

ESI-MS: found: 392.2 (M+H⁺); calculated: 391.46 g/mol.

Example 168 Compound 165

m.p.: 268° C.

ESI-MS: found: 432.2 (M+H⁺); calculated: 431.54 g/mol.

Example 169 Compound 166

m.p.: 278° C.

ESI-MS: found: 409.4 (M+H⁺); calculated: 409.30 g/mol.

Example 170 Compound 167

m.p.: 253° C.

ESI-MS: found: 343.0 (M+H⁺); calculated: 342.79 g/mol.

Example 171 Compound 168

m.p.: 289° C.

ESI-MS: found: 375.4 (M+H⁺); calculated: 374.47 g/mol.

Example 172 Compound 169

m.p.: 228° C.

ESI-MS: found: 351.8 (M+H⁺); calculated: 351.41 g/mol.

Example 173 Compound 170

m.p.: 243° C.

ESI-MS: found: 350.9 (M+H⁺); calculated: 350.38 g/mol.

Example 174 Compound 172

m.p.: 242-244° C.

ESI-MS: found: 326.1 (M+H⁺); calculated: 325.33 g/mol.

Example 175 Compound 173

m.p.: 215-218° C.

ESI-MS: found: 374.1 (M+H⁺); calculated: 373.80 g/mol.

Example 176 Compound 176

m.p.: 234-237° C.

ESI-MS: found: 389.2 (M+H⁺); calculated: 388.39 g/mol.

Example 177 Compound 177

m.p.: 234-237° C.

ESI-MS: found: 351.9 (M+H⁺); calculated: 351.41 g/mol.

Example 178 Compound 178

m.p.: 227-228° C.

ESI-MS: found: 308.0 (M+H⁺); calculated: 307.36 g/mol.

Example 179 Compound 179

m.p.: >320° C.

ESI-MS: found: 309.2 (M+H⁺); calculated: 308.34 g/mol.

Example 180 Compound 180

m.p.: >320° C.

ESI-MS: found: 323.0 (M+H⁺); calculated: 322.37 g/mol.

Example 181 Compound 181

m.p.: >240° C.

ESI-MS: found: 338.2 (M+H⁺); calculated: 337.38 g/mol.

Example 182 Compound 182

m.p.: 277-279° C.

ESI-MS: found: 310.2 (M+H⁺); calculated: 309.33 g/mol.

Example 183 Compound 183

m.p.: >250° C.

ESI-MS: found: 342.8 (M+H⁺); calculated: 341.39 g/mol.

Example 184 Compound 194

m.p.: 305-308° C.

ESI-MS: found: 367.2 (M+H⁺); calculated: 366.38 g/mol.

Example 185 Compound 195

m.p.: 248° C.

ESI-MS: found: 383.2 (M+H⁺); calculated: 382.45 g/mol.

Example 186 Compound 197

m.p.: 211° C.

ESI-MS: found: 341.2 (M+H⁺); calculated: 340.41 g/mol.

Example 187 Compound 198

m.p.: 258° C.

ESI-MS: found: 341.1 (M+H⁺); calculated: 340.41 g/mol.

Example 188 Compound 200

m.p.: 238° C.

ESI-MS: found: 415.3 (M+H⁺); calculated: 414.49 g/mol.

Example 189 Compound 201

m.p.: 260° C.

ESI-MS: found: 373.1 (M+H⁺); calculated: 372.81 g/mol.

Example 190 Compound 202

m.p.: 225° C.

ESI-MS: found: 389.2 (M+H⁺); calculated: 388.88 g/mol.

Example 191 Compound 203

m.p.: 166° C.

ESI-MS: found: 371.2 (M+H⁺); calculated: 370.44 g/mol.

Example 192 Compound 205

m.p.: 166° C.

ESI-MS: found: 371.2 (M+H⁺); calculated: 370.44 g/mol.

Example 193 Compound 207

m.p.: 236° C.

ESI-MS: found: 432.2 (M+H⁺); calculated: 431.54 g/mol.

Example 194 Compound 208

m.p.: 203° C.

ESI-MS: found: 375.2 (M+H⁺); calculated: 374.85 g/mol.

Example 195 Compound 209

m.p.: 255° C.

ESI-MS: found: 353.1 (M+H⁺); calculated: 352.40 g/mol.

Example 196 Compound 210

m.p.: 148° C.

ESI-MS: found: 369.0 (M+H⁺); calculated: 368.46 g/mol.

Example 197 Compound 217

m.p.: 185° C.

ESI-MS: found: 359.0 (M+H⁺); calculated: 358.86 g/mol.

Example 198 Compound 221

m.p.: 189° C.

ESI-MS: found: 355.2 (M+H⁺); calculated: 354.44 g/mol.

Example 199 Compound 225

m.p.: 243-245° C.

ESI-MS: found: 303.2 (M+H⁺); calculated: 302.34 g/mol.

Example 200 Compound 227

m.p.: 214-216° C.

ESI-MS: found: 316.3 (M+H⁺); calculated: 315.34 g/mol.

Example 201 Compound 231

m.p.: 201-203° C.

ESI-MS: found: 287.1 (M+H⁺); calculated: 286.34 g/mol.

Example 202 Compound 233

m.p.: 199-201° C.

ESI-MS: found: 330.3 (M+H⁺); calculated: 329.41 g/mol.

Example 203 Compound 235

m.p.: 249-251° C.

ESI-MS: found: 317.2 (M+H⁺); calculated: 316.36 g/mol.

Example 204 Compound 239

m.p.: 211-213° C.

ESI-MS: found: 323.2 (M+H⁺); calculated: 322.37 g/mol.

Example 205 Compound 241

ESI-MS: found: 337.2 (M+H⁺); calculated: 336.40 g/mol.

Example 206 Compound 255

ESI-MS: found: 392.4 (M+H⁺); calculated: 391.50 g/mol.

Example 207 Compound 257

m.p.: 216° C.

ESI-MS: found: 418.1 (M+H⁺); calculated: 417.54 g/mol.

Example 208 Compound 329

m.p.: >220° C.

ESI-MS: found: 359.3 (M+H⁺); calculated: 358.86 g/mol.

Example 209 Compound 331

m.p.: 258° C.

ESI-MS: found: 355.3 (M+H⁺); calculated: 354.44 g/mol.

Example 210 Compound 332

m.p.: 232° C.

ESI-MS: found: 355.1 (M+H⁺); calculated: 354.44 g/mol.

Example 211 Compound 336

m.p.: 255° C.

ESI-MS: found: 381.2 (M+H⁺)-free Base; calculated: 416.91 g/mol.

Example 212 Compound 341

m.p.: 235° C.

ESI-MS: found: 477.4 (M+H⁺)— free base; calculated: 513.00 g/mol.

Example 213 Compound 374

m.p.: 215° C.

ESI-MS: found: 352.0 (M+H⁺); calculated: 351.41 g/mol.

Example 214 Compound 378

m.p.: 225° C.

ESI-MS: found: 336.8 (M+H⁺); calculated: 336.44 g/mol.

Example 215 Compound 380

ESI-MS: found: 339.2 (M+H⁺); calculated: 338.37 g/mol.

Example 216 Compound 394

m.p.: 272° C.

ESI-MS: found: 339.2 (M+H⁺); calculated: 338.37 g/mol.

Example 217 Compound 398

m.p.: 210° C.

ESI-MS: found: 336.8 (M+H⁺); calculated: 336.40 g/mol.

Example 218 Compound 399

m.p.: 215° C.

ESI-MS: found: 353.1 (M+H⁺); calculated: 352.46 g/mol.

Example 219 Compound 433

m.p.: 265° C.

ESI-MS: found: 361.2 (M+H⁺); calculated: 360.39 g/mol.

Example 220 Compound 434

m.p.: 324-329° C.

ESI-MS: found 387.1 (M+H⁺); calculated: 386.80 g/mol.

Example 221 Compound 441

m.p.: 220° C.

ESI-MS: found: 375.3 (M+H⁺); calculated: 374.85 g/mol.

Example 222 Compound 443

m.p.: 270° C.

ESI-MS: found: 394.1 (M+H⁺); calculated: 393.30 g/mol.

Example 223 Compound 446

m.p.: 222° C.

ESI-MS: found: 353.0 (M+H⁺); calculated: 352.40 g/mol.

Example 224 Compound 465

m.p.: 277° C.

ESI-MS: found: 428.3 (M+H⁺); calculated: 427.75 g/mol.

Example 225 Compound 467

m.p.: 232° C.

ESI-MS: found: 367.1 (M+H⁺); calculated: 366.45 g/mol.

Example 226 Compound 489

m.p.: 260° C.

ESI-MS: found: 388.2 (M+H⁺); calculated: 387.40 g/mol.

Example 227 Compound 491

m.p.: 250° C.

ESI-MS: found: 386.4 (M+H⁺); calculated: 385.41 g/mol.

Example 228 Compound 501

m.p.: 243° C.

ESI-MS: found: 429.2 (M+H⁺); calculated: 428.51 g/mol.

Example 229 Compound 509

m.p.: 246° C.

ESI-MS: found: 455.1 (M+H⁺); calculated: 454.55 g/mol.

Example 230 Compound 518

m.p.: 245-238° C.

ESI-MS: found: 370.4 (M+H⁺); calculated: 369.45 g/mol.

Example 231 Compound 519

m.p.: 233-235° C.

ESI-MS: found: 396.3 (M+H⁺); calculated: 395.48 g/mol.

Example 232 Compound 521

m.p.: 261-262° C.

ESI-MS: found: 368.2 (M+H⁺); calculated: 367.43 g/mol.

Example 233 Compound 524

m.p.: 253-254° C.

ESI-MS: found: 410.4 (M+H⁺); calculated: 409.51 g/mol.

Example 234 Compound 526

m.p.: 279-280° C.

ESI-MS: found: 342.0 (M+H⁺); calculated: 341.39 g/mol.

Example 235 Compound 529

m.p.: 224-226° C.

ESI-MS: found: 422.3 (M+H⁺); calculated: 421.84 g/mol.

Example 236 Compound 533

ESI-MS: found: 402.4 (M+H⁺); calculated: 401.42 g/mol.

Example 237 Compound 541

ESI-MS: found: 456.4 (M+H⁺); calculated: 455.39 g/mol.

Example 238 Compound 551

m.p.: 265-268° C.

ESI-MS: found: 392.2 (M+H⁺); calculated: 392.24 g/mol.

Example 239 Compound 552

m.p.: 259-261° C.

ESI-MS: found: 392.2 (M+H⁺); calculated: 392.24 g/mol.

Example 240 Compound 553

m.p.: 251-253° C.

ESI-MS: found: 406.2 (M+H⁺); calculated: 406.27 g/mol.

Example 241 Compound 554

m.p.: 226-230° C.

ESI-MS: found: 530.2 (M+H⁺); calculated: 529.30 g/mol.

Example 242 Compound 555

m. p.: 259-262° C.

ESI-MS: found: 469.3 (M+H⁺); calculated: 469.33 g/mol.

Example 243 Compound 556

m.p.: 261-263° C.

ESI-MS: found: 460.3 (M+H⁺); calculated: 460.36 g/mol.

Example 244 Compound 557

m.p.: 247-249° C.

ESI-MS: found: 364.2 (M+H⁺); calculated: 364.19 g/mol.

Example 245 Compound 558

m.p.: 272-275° C.

ESI-MS: found: 432.2 (M+H⁺); calculated: 432.31 g/mol.

Example 246 Compound 559

m.p.: 289-291° C.

ESI-MS: found: 444.3 (M+H⁺); calculated: 444.25 g/mol.

Example 247 Compound 560

m.p.: 253-255° C.

ESI-MS: found: 432.3 (M+H⁺); calculated: 432.29 g/mol.

Example 248 Compound 561

m.p.: >300° C.

ESI-MS: found: 471.0 (M+H⁺); calculated: 471.26 g/mol.

Example 249 Compound 562

m.p.: 257-260° C.

ESI-MS: found: 445.1 (M+H⁺); calculated: 445.26 g/mol.

Example 250 Compound 563

m.p.: 262-264° C.

ESI-MS: found: 418.1 (M+H⁺); calculated: 418.28 g/mol.

Example 251 Compound 564

m.p.: 280-282° C.

ESI-MS: found: 454.3 (M+H⁺); calculated: 454.32 g/mol.

Example 252 Compound 565

m.p.: >300° C.

ESI-MS: found: 521.3 (M+H⁺); calculated: 521.32 g/mol.

Example 253 Compound 566

m.p.: 253-255° C.

ESI-MS: found: 340.1 (M+H⁺); calculated: 339.35 g/mol.

Example 254 Compound 567

m.p.: 233-236° C.

ESI-MS: found: 368.2 (M+H⁺); calculated: 367.41 g/mol.

Example 255 Compound 568

m.p.: 230-233° C.

ESI-MS: found: 382.2 (M+H⁺); calculated: 381.43 g/mol.

Example 256 Compound 569

m.p.: 262-263° C.

ESI-MS: found: 445.3 (M+H⁺); calculated: 444.49 g/mol.

Example 257 Compound 570

m.p.: 246-248° C.

ESI-MS: found: 368.2 (M+H⁺); calculated: 367.41 g/mol.

Example 258 Compound 571

m.p.: 262-264° C.

ESI-MS: found: 408.3 (M+H⁺); calculated: 407.47 g/mol.

Example 259 Compound 572

m.p.: 269-271° C.

ESI-MS: found: 420.4 (M+H⁺); calculated: 419.41 g/mol.

Example 260 Compound 573

m.p.: 265-267° C.

ESI-MS: found: 421.3 (M+H⁺); calculated: 420.43 g/mol.

Example 261 Compound 574

m.p.: 188-191° C.

ESI-MS: found: 402.2 (M+H⁺); calculated: 401.42 g/mol.

Example 262 Compound 575

m.p.: 236-238° C.

ESI-MS: found: 366.1 (M+H⁺); calculated: 365.39 g/mol.

Example 263 Compound 576

m.p.: 261-264° C.

ESI-MS: found: 394.3 (M+H⁺); calculated: 393.44 g/mol.

Example 264 Compound 577

m.p.: 254-257° C.

ESI-MS: found: 430.2 (M+H⁺); calculated: 429.48 g/mol.

Example 265 Compound 578

m.p.: 263-266° C.

ESI-MS: found: 416.2 (M+H⁺); calculated: 415.48 g/mol.

Example 266 Compound 579

m.p.: 279-283° C.

ESI-MS: found: 497.1 (M+H⁺); calculated: 496.48 g/mol.

Example 267 Compound 580

m.p.: 248-251° C.

ESI-MS: found: 402.1 (M+H⁺); calculated: 401.42 g/mol.

Example 268 Compound 581

m.p.: 239-242° C.

ESI-MS: found: 505.0 (M+H⁺); calculated: 504.47 g/mol.

Example 269 Compound 582

ESI-MS: found: 382.3 (M+H⁺); calculated: 381.43 g/mol.

Example 270 Compound 583

m.p.: 273-275° C.

ESI-MS: found: 429.2 (M+H⁺); calculated: 428.49 g/mol.

Example 271 Compound 584

m.p.: 247-250° C.

ESI-MS: found: 392.4 (M+H⁺); calculated: 391.47 g/mol.

Example 272 Compound 585

ESI-MS: found: 351.9 (M+H⁺); calculated: 351.41 g/mol.

Example 273 Compound 586

m.p.: 240-241° C.

ESI-MS: found: 351.9 (M+H⁺); calculated: 351.41 g/mol.

Example 274 Compound 587

m.p.: 210-212° C.

ESI-MS: found: 350.1 (M+H⁺); calculated: 349.39 g/mol.

Example 275 Compound 588

m.p.: 267-269° C.

ESI-MS: found: 414.2 (M+H⁺); calculated: 413.48 g/mol.

Example 276 Compound 589

m.p.: 251-253° C.

ESI-MS: found: 489.0 (M+H⁺); calculated: 488.47 g/mol.

Example 277 Compound 590

m.p.: 242-244° C.

ESI-MS: found: 405.2 (M+H⁺); calculated: 404.43 g/mol.

Example 278 Compound 591

ESI-MS: found: 324.1 (M+H⁺); calculated: 323.35 g/mol.

Example 279 Compound 592

ESI-MS: found: 351.9 (M+H⁺); calculated: 351.41 g/mol.

Example 280 Compound 593

ESI-MS: found: 366.0 (M+H⁺); calculated: 365.43 g/mol.

Example 281 Compound 594

ESI-MS: found: 404.3 (M+H⁺); calculated: 403.42 g/mol.

Example 282 Compound 595

m.p.: 271-273° C.

ESI-MS: found: 386.2 (M+H⁺); calculated: 385.43 g/mol.

Example 283 Compound 596

m.p.: 263° C.

ESI-MS: found: 422.2 (M+H⁺); calculated: 421.54 g/mol.

Example 284 Compound 597

m.p.: 221° C.

ESI-MS: found: 380.2 (M+H⁺); calculated: 379.46 g/mol.

Example 285 Compound 598

m.p.: 232° C.

ESI-MS: found: 380.1 (M+H⁺); calculated: 379.46 g/mol.

Example 286 Compound 599

m.p.: 233° C.

ESI-MS: found: 394.1 (M+H⁺); calculated: 393.49 g/mol.

Example 287 Compound 600

m.p.: 244-246° C.

ESI-MS: found: 406.3 (M+H⁺); calculated: 405.39 g/mol.

Example 288 Compound 601

ESI-MS: found: 460.5 (M+H⁺); calculated: 459.46 g/mol.

Example 289 Compound 602

m.p.: 287-290° C.

ESI-MS: found: 431.2 (M+H⁺); calculated: 430.47 g/mol.

Example 290 Compound 603

m.p.: 233-236° C.

ESI-MS: found: 428.3 (M+H⁺); calculated: 427.46 g/mol.

Example 291 Compound 604

m.p.: 232-234° C.

ESI-MS: found: 422.4 (M+H⁺); calculated: 421.50 g/mol.

Example 292 Compound 605

m.p.: 252-254° C.

ESI-MS: found: 446.4 (M+H⁺); calculated: 445.52 g/mol.

Example 293 Compound 606

m.p.: 210-212° C.

ESI-MS: found: 529.4 (M+H⁺); calculated: 528.57 g/mol.

Example 294 Compound 607

m.p.: 260-263° C.

ESI-MS: found: 474.5 (M+H⁺); calculated: 473.49 g/mol.

Example 295 Compound 608

ESI-MS: found: 408.4 (M+H⁺); calculated: 407.47 g/mol.

Example 296 Compound 609

m.p.: 257-259° C.

ESI-MS: found: 444.3 (M+H⁺); calculated: 443.49 g/mol.

Example 297 Compound 610

ESI-MS: found: 491.5 (M+H⁺); calculated: 490.44 g/mol.

Example 298 Compound 611

m.p.: 245-248° C.

ESI-MS: found: 389.4 (M+H⁺); calculated: 388.39 g/mol.

Example 299 Compound 612

m.p.: 272-273° C.

ESI-MS: found: 408.4 (M+H⁺); calculated: 407.47 g/mol.

Example 300 Compound 613

m.p.: 232-236° C.

ESI-MS: found: 424.4 (M+H⁺); calculated: 423.51 g/mol.

Example 301 Compound 614

m.p.: 216-219° C.

ESI-MS: found: 394.4 (M+H⁺); calculated: 393.43 g/mol.

Example 302 Compound 615

ESI-MS: found: 471.4 (M+H⁺); calculated: 470.53 g/mol.

Example 303 Compound 616

m.p.: 247-250° C.

ESI-MS: found: 433.3 (M+H⁺); calculated: 432.39 g/mol.

Example 304 Compound 617

m.p.: 220-222° C.

ESI-MS: found: 433.4 (M+H⁺); calculated: 432.39 g/mol.

Example 305 Compound 618

m.p.: 274-276° C.

ESI-MS: found: 433.1 (M+H⁺); calculated: 432.39 g/mol.

Example 306 Compound 619

m.p.: 214-217° C.

ESI-MS: found: 453.4 (M+H⁺); calculated: 452.43 g/mol.

Example 307 Compound 620

m.p.: 207-210° C.

ESI-MS: found: 486.3 (M+H⁺); calculated: 485.55 g/mol.

Example 308 Compound 621

m.p.: 248-251° C.

ESI-MS: found: 441.5 (M+H⁺); calculated: 440.46 g/mol.

Example 309 Compound 622

m.p.: 290-293° C.

ESI-MS: found: 483.5 (M+H⁺); calculated: 482.45 g/mol.

Example 310 Compound 623

m.p.: 263-265° C.

ESI-MS: found: 453.4 (M+H⁺); calculated: 452.47 g/mol.

Example 311 Compound 624

m.p.: 242-245° C.

ESI-MS: found: 432.2 (M+H⁺); calculated: 431.45 g/mol.

Example 312 Compound 625

m.p.: 235-238° C.

ESI-MS: found: 418.1 (M+H⁺); calculated: 417.42 g/mol.

Example 313 Compound 626

m.p.: 259-261° C.

ESI-MS: found: 413.3 (M+H⁺); calculated: 412.41 g/mol.

Example 314 Compound 627

m.p.: 234-235° C.

ESI-MS: found: 396.4 (M+H⁺); calculated: 395.46 g/mol.

Example 315 Compound 628

m.p.: 233-235° C.

ESI-MS: found: 478.4 (M+H⁺); calculated: 477.61 g/mol.

Example 316 Compound 629

m.p.: 233-236° C.

ESI-MS: found: 430.3 (M+H⁺); calculated: 429.48 g/mol.

Example 317 Compound 630

m.p.: 208-210° C.

ESI-MS: found: 444.4 (M+H⁺); calculated: 443.50 g/mol.

Example 318 Compound 631

m.p.: 223-226° C.

ESI-MS: found: 368.2 (M+H⁺); calculated: 367.41 g/mol.

Example 319 Compound 632

m.p.: 214-216° C.

ESI-MS: found: 368.2 (M+H⁺); calculated: 367.41 g/mol.

Example 320 Compound 633

ESI-MS: found: 464.4 (M+H⁺); calculated: 463.49 g/mol.

Example 321 Compound 634

ESI-MS: found: 470.1 (M+H⁺); calculated: 469.42 g/mol.

Example 322 Compound 635

m.p.: 226-228° C.

ESI-MS: found: 444.1 (M+H⁺); calculated: 443.50 g/mol.

Example 323 Compound 636

ESI-MS: found: 436.1 (M+H⁺); calculated: 435.87 g/mol.

Example 324 Compound 637

m.p.: >270° C.

ESI-MS: found: 344.6 (M+H⁺); calculated: 343.77 g/mol.

Example 325 Compound 638

ESI-MS: found: 340.1 (M+H⁺); calculated: 339.35 g/mol.

Example 326 Compound 639

m.p.: 250-252° C.

ESI-MS: found: 416.9 (M+H⁺); calculated: 416.77 g/mol.

Example 327 Compound 640

m.p.: 262° C.

ESI-MS: found: 396.2 (M+H⁺); calculated: 395.31 g/mol.

Example 328 Compound 641

m.p.: 291° C.

ESI-MS: found: 388.2 (M+H⁺); calculated: 388.22 g/mol.

Example 329 Compound 642

m.p.: 266° C.

ESI-MS: found: 358.2 (M+H⁺); calculated: 357.80 g/mol.

Example 330 Compound 643

m.p.: 263° C.

ESI-MS: found: 422.2 (M+H⁺); calculated: 421.54 g/mol.

Example 331 Compound 644

m.p.: 225° C.

ESI-MS: found: 354.1 (M+H⁺); calculated: 353.34 g/mol.

Example 332 Compound 647

ESI-MS: found: 310.2 (M+H⁺); calculated: 309.40 g/mol.

Example 333 Compound 648

ESI-MS: found: 355.3 (M+H⁺); calculated: 354.44 g/mol.

Example 334 Compound 649

ESI-MS: found: 368.1 (M+H⁺); calculated: 367.47 g/mol.

Example 335 Compound 650

m.p.: 218-219° C.

ESI-MS: found: 400.2 (M+H⁺); calculated: 399.47 g/mol.

Example 336 Compound 651

m.p.: 230-231° C.

ESI-MS: found: 324.1 (M+H⁺); calculated: 323.42 g/mol.

Example 337 Compound 652

m.p.: 213-215° C.

ESI-MS: found: 384.3 (M+H⁺); calculated: 383.47 g/mol.

Example 338 Compound 653

m.p.: 250-251° C.

ESI-MS: found: 438.4 (M+H⁺); calculated: 437.57 g/mol.

Example 339 Compound 654

m.p.: 238-240° C.

ESI-MS: found: 462.4 (M+H⁺); calculated: 461.59 g/mol.

Example 340 Compound 655

ESI-MS: found: 354.0 (M+H⁺); calculated: 353.38 g/mol.

Example 341 Compound 660

m.p.: 168-170° C.

ESI-MS: found: 387.1 (M+H⁺); calculated: 386.41 g/mol.

Example 342 Compound 661

ESI-MS: found: 393.3 (M+H⁺); calculated: 392.46 g/mol.

Example 343 Compound 686

ESI-MS: found: 368.1 (M+H⁺); calculated: 367.41 g/mol.

Example 344 Compound 690

m.p.: 248° C.

ESI-MS: found: 469.2 (M+H⁺); calculated: 468.58 g/mol.

Example 345 Compound 691

m.p.: 250° C.

ESI-MS: found: 497.3 (M+H⁺); calculated: 496.63 g/mol.

Example 346 Compound 692

m.p.: 258-261° C.

ESI-MS: found: 401.1 (M+H⁺); calculated: 400.46 g/mol.

Example 347 Compound 693

m.p.: 230-234° C.

ESI-MS: found: 427.3 (M+H⁺); calculated: 426.50 g/mol.

Example 348 Compound 694

m.p.: 218-220° C.

ESI-MS: found: 443.2 (M+H⁺); calculated: 442.54 g/mol.

Example 349 Compound 695

m.p.: 247° C.

ESI-MS: found: 482.3 (M+H⁺); calculated: 481.53 g/mol.

Example 350 Compound 696

m.p.: 347° C.

ESI-MS: found: 483.1 (M+H⁺); calculated: 482.61 g/mol.

Example 351 Compound 697

m.p.: 250-252° C.

ESI-MS: found: 477.0 (M+H⁺); calculated: 476.56 g/mol.

Example 352 Compound 698

m.p.: 248-250° C.

ESI-MS: found: 491.1 (M+H⁺); calculated: 490.59 g/mol.

Example 353 Compound 699

m.p.: 197-200° C.

ESI-MS: found: 491.3 (M+H⁺); calculated: 490.59 g/mol.

Example 354 Compound 700

m.p.: 206° C.

ESI-MS: found: 498.1 (M+H⁺); calculated: 497.62 g/mol.

Example 355 Compound 701

m.p.: 255° C.

ESI-MS: found: 495.1 (M+H⁺); calculated: 494.55 g/mol.

Example 356 Compound 702

m.p.: 210° C.

ESI-MS: found: 457.4 (M+H⁺); calculated: 456.57 g/mol.

Example 357 Compound 703

m.p.: 196° C.

ESI-MS: found: 500.2 (M+H⁺); calculated: 499.59 g/mol.

Example 358 Compound 704

m.p.: 195-198° C.

ESI-MS: found: 505.3 (M+H⁺); calculated: 504.61 g/mol.

Example 359 Compound 705

m.p.: 243-245° C.

ESI-MS: found: 445.4 (M+H⁺); calculated: 444.51 g/mol.

Example 359 Compound 706

m.p.: 222° C.

ESI-MS: found: 428.9 (M+H⁺); calculated: 428.51 g/mol.

Example 360 Compound 707

m.p.: 248° C.

ESI-MS: found: 427.3 (M+H⁺); calculated: 426.50 g/mol.

Example 361 Compound 708

m.p.: 228° C.

ESI-MS: found: 467.3 (M+H⁺); calculated: 466.52 g/mol.

Example 362 Compound 709

m.p.: 244° C.

ESI-MS: found: 487.2 (M+H⁺); calculated: 486.55 g/mol.

Example 363 Compound 710

m.p.: 246° C.

ESI-MS: found: 459.4 (M+H⁺); calculated: 458.54 g/mol.

Example 364 Compound 711

m.p.: 248° C.

ESI-MS: found: 491.4 (M+H⁺); calculated: 490.59 g/mol.

Example 365 Compound 733

m.p.: 110° C.

ESI-MS: found: 356.0 (M+H⁺); calculated: 355.40 g/mol.

II) Biological effects of the compounds of the invention II.1) Cell-FreeKinase Assays (by Means of Alpha Technology)

The inhibitory effect of the compounds of the invention was tested onvarious human serine/threonine kinases, tyrosine kinases and lipidkinases in enzymatic assays.

Recombinant human kinases, for example PI3Kalpha, -beta, -gamma, -delta,Erk2, p38alpha, p38gamma, Jnk1, Jnk2 and others were used, in some casesas full-length kinases, in some cases as truncated fragments—but atleast consisting of the functional kinase domains. The commercial kinaseproteins (Proqinase, Upstate) were used as recombinant fusion proteinswith GST (glutathione S-transferase) tag or His tag. Depending on thesubstrate type, the different kinase reactions were quantified bysuitable ALPHA™ beads (PerkinElmer).

Testing

The kinase assays for PI3K and Erk are described in detail and selectedtest results are cited below. To determine the IC₅₀ value, the potentialinhibitor substances were investigated at 10 half-logarithmicallygraduated concentrations of 3.16 nM-100 μM.

-   -   a) PI3K-ALPHA (e.g. PI3Kalpha): The test substance, 1 ng of        PI3Kalpha (#14-602, Upstate), 100 μM ATP and 20 μM PIP₂        substrate (#P4508, Echelon) were incubated on a 384-well        Optiplate (Perkin Elmer) for 60 minutes in 50 mM Hepes, 50 mM        NaCl, 5 mM MgCl₂, 0.05% Chaps, 5 mM DTT at pH 7.4. Subsequently,        the kinase reaction was stopped by adding the ALPHA bead mix (10        μg/ml, #6760603/PerkinElmer), preincubated with 1 nM GST:Grp1        fusion protein (Upstate) and 15 nM biotinylated PIP3        (#C-39B6/Echelon) in 50 mM Hepes, 50 mM NaCl, 50 mM EDTA and        0.1% BSA, and left to stand overnight.    -   b) Erk2-ALPHA: The test substance, 0.625 ng of Erk2 (#14-173,        Upstate), 10 μM ATP and 15 nM biotinylated MBP (myelin basic        protein) substrate were incubated on a 384-well Optiplate        (Perkin Elmer) in a volume of 15 μl for 1 h in 25 mM Tris, 10 mM        MgCl₂, 0.1% Tween-20, 100 μM NaVO₄, 2 mM DTT at pH 7.5. The        kinase reaction was stopped by adding 10 μl of the ALPHA bead        mix (10 μg/ml, #6760617/PerkinElmer), pre-incubated with        anti-phospho MBP antibody (320 μM, #05-429/Up-state), in 25 mM        Tris, 200 mM NaCl, 100 mM EDTA and 0.3% BSA, and left to stand        overnight.

The luminiscence was detected the next morning in a Fusion™alphainstrument (Perkin Elmer).

Evaluation

The calculation of % inhibition values per substance concentration wasdone by means of the following formula from the raw data determined inthe Fusion™alpha:

${\% \mspace{14mu} {kinase}\mspace{14mu} {inhibition}_{({sample})}} = {100 - \left( {100 \times \frac{{mean}_{({sample})} - {mean}_{({0\% \mspace{14mu} {control}})}}{{mean}_{({100\% \mspace{14mu} {control}})} - {mean}_{({0\% \mspace{14mu} {control}})}}} \right)}$

The controls were determined 8 fold and the substance samples 2 fold. 0%control contained neither any ATP nor any substrate. The 100% controlcontained no test substance. The IC₅₀ values were determined withGraphPadPrism.

The compounds of the invention exhibited effective inhibition ofPI3Kalpha, Erk2, p38alpha and Jnk1+Jnk2 with IC₅₀ values of <500 nM (seeTable 1).

TABLE 1 PI3Kalpha and MAPK kinase assay test results (IC₅₀ [μM] at 10 μMor 100 μM* ATP) Compound PI3Kalpha* Erk2 p38alpha Jnk1 + Jnk2 5<0.5 >100 >100 >10 20 <1 >100 >100 >100 30 <1 <10 <10 <31.6 46 <5<0.5 >100 <1 50 <1 >100 >100 >100 54 <5 <0.5 >100 <31.6 55 <5 >100<10 >100 56 <5 <10 <10 >10 73 <5 >100 >10 >100 147 <1 >100 >100 >31.6160 <1 <31.6 <50 >100 173 <1 <50 <50 <31.6 176 <1 >31.6 <50 <50 181<5 >100 <50 >100 509 <1 >100 >100 >100 526 <1 >100 <50 >100 553<5 >100 >100 <100 563 <1 >100 — — 566 <5 >100 >31.6 >100 614 <1 <31.6<10 <31.6 637 <5 >100 >100 >100

Especially compound 5 and derivatives are characterized by low IC₅₀values against PI3K and high selectivity against the other kinases.

Also pyridopyrazines, substituted by —NH-heteroaryl at the pyrazine ring(for example, compounds 50, 55, 56 and 73), show PI3K inhibition, but noor only moderate MAPK inhibition.

Pyridopyrazines, substituted by heteroaryl at the pyrazine ring (forexample, compounds 46 and 54) exhibit a dual mode of kinase inhibitionat least, namely an inhibition of PI3K and Erk2.

II.2) Cellular Assay: Testing for Anti-Proliferate Activity (XTT Assay)

The principle of this test is based on the intracellular reduction ofthe tetrazolium dye XTT (sodium3′-[1-(phenylaminocarbonyl)-3,4-tetrazolium]bis(4-methoxy-6-nitro)benzenesulphonicacid, Sigma) to a formazan dye by mitochondrial dehydrogenases. The dyeis formed only by metabolically active cells. Its photometricallymeasurable intensity is a quantitative indicator for the presence ofliving cells. The reduction in the dye formation as a result ofincubation of the cells with substances serves as a parameter for theanti-proliferative activity.

Testing

The tumour cell lines (ATCC) were seeded in 96-well microtitre plates ina defined cell count (5000 cells/well for Hct116; 10000 cells/well forMDA MB468), and incubated overnight at 37° C., 5% CO₂ and 95% airhumidity. The test substances were made up as stock solutions (10 mM) inDMSO. To determine the EC₅₀ values, the potential inhibitor substanceswere added to the cells in quarter-logarithmically graded dilutions, soas to result in final concentrations of 0.28 μM-50 μM. The cell plateswere then incubated for 45 h at 37° C., 5% CO₂ and 95% air humidity.

For the detection reaction, the XTT substrate was mixed with PMS(N-methyldibenzopyrazine methylsulphate, Sigma) and added to the cells,to result in a final concentration of 325 μg of XTT/ml and 2.5 μgPMS/ml. The mixture was then incubated for 3 h at 37° C., 95% airhumidity. Subsequently the formazan salt formed by cellulardehydrogenases was quantified at an absorption of 490 nm.

Evaluation

The evaluation of the % inhibition values was done by means of thefollowing formula from the values for the optical densities measured ineach case at 490 nm:

${\% \mspace{14mu} {inhibition}\mspace{14mu} {of}\mspace{14mu} {cell}\mspace{14mu} {proliferation}_{({sample})}} = {100 - \left( {100 \times \frac{{mean}_{({sample})} - {mean}_{({0\% \mspace{14mu} {control}})}}{{mean}_{({100\% \mspace{14mu} {control}})} - {mean}_{({0\% \mspace{14mu} {control}})}}} \right)}$

The controls were determined 8 fold, the substance samples 2 fold. 0%control contained no cells and the 100% control contained no testsubstance. The EC₅₀ values were determined with GraphPadPrism.

The compounds of the invention exhibited effective inhibition of cellproliferation in some cases with EC₅₀ values<1 μM (see Table 2).

TABLE 2 XTT assay test results (EC50 [μM]) Compound MDA-MB468 Hct116 5<1 <2 46 <10 <10 50 <10 <5 54 <5 <5 55 <5 <5 56 <5 <10 73 <5 <5 89 <5 <5113 <5 <5 126 <5 <5 134 <5 <5 138 <10 <10 140 <5 <5 147 <5 <5 148 <5 <10150 <5 <5 152 <10 <10 160 <1 <1 173 <1 <1 176 <1 <1 181 <10 <10 509 <5<5 526 <1 <5 553 <5 <5 563 <1 <1 566 <5 <5 614 <5 <5 637 <10 <10

Especially compound 5 and derivatives display high anti-proliferativepotencies against human tumor cell lines, as they show EC₅₀ values inthe nanomolar range

II.3) Cellular Assay: Testing of Substrate Inhibition (Western Blotting)

This method enables a statement of whether the kinase modulatorinvestigated achieves the desired effect in a cellular context too,i.e., in this case, a substrate protein downstream of the target kinaseis examined for its phosphorylation status. To this end, the cellsincubated with substance are lysed and the overall protein is separatedon a reducing polyacrylamide gel. Subsequently, the proteins aretransferred to a PVDF membrane by Western blotting and the substratebands sought are made visible with specific antibodies and a suitabledetection method. The substrate proteins down-stream of the targetkinases are detected simultaneously with an anti-phospho antibody whichis specific in each case and a total antibody which recognizes thesubstrate total protein. The duplex technology of the ODYSSEY imager(LiCOR) enables this simultaneous measurement. The intensity of thetotal substrate bands is employed to normalize and quantify thephosphorylation inhibition or activation.

Testing

Suitable tumor cell lines (e.g. BxPC3, Hct116 or MDA MB468) were seededinto 6-well microtitre plates in a defined cell count (e.g. 350 000cells/well for BxPC3 and Hct116) in the particular standard completemedia and then incubated overnight at 37° C., 5% CO₂ and 95% airhumidity. Afterwards, the cells were incubated for 24 h underserum-reduced conditions, i.e. in the particular medium except at only0.25% serum. The test substances were made up as stock solutions (10 mM)in DMSO and incubated with the cells at final concentrations of 5, 15.8and 50 μM for 5 h. This was followed by cell lysis in 25 mM Tris, 150 mMNaCl, 10 mM sodium pyrophosphate, 2 mM EGTA, 25 mMbeta-glycerophosphate, 25 mM NaF, 10% glycerol, 0.75% NP-40, 100 μMNaVO₄ buffer. After protein quantification using the BCA (bicinchonicacid protein assay kit, Sigma) assay, amounts of protein of about 20 μgper track were separated on a Lammli polyacrylamide gel and thentransferred onto a PVDF membrane (Millipore) by semi-dry Westernblotting at 0.8 mA/cm² for 1 h. This was followed by prehybridization ofthe membrane for 1 hour in I-block reagent (Applied Biosystems) andovernight simultaneous incubation with the specific antibodies. Todetermine the Erk and PI3K inhibition, the next substrates Rsk1downstream were detected with the total antibody (Rsk #sc-231g C-21,Santa Cruz) and the phospho antibody (Phospho-p90RSK (S380) #9341, NEBCell Signalling) and Akt with the total antibody (Akt1 #sc-1618 C-20,Santa Cruz) and the phospho antibody (Phospho-Akt (Ser 473) #9271, NEBCell Signaling). After the membrane had been washed, the secondaryantibodies were incubated with anti-rabbit IR Dye 800 (#611-732-127,Rockland) for the phospho antibodies and anti-goat Alexa Fluor 680(#A-21081, Molecular samples) for the total protein antibodies. Afterincubation for 30 min at room temperature in the dark, the hybridizationof the detection antibody was detected on the membrane by scanning in anODYSSEY imager (LiCOR).

Evaluation

At concentrations of 5-50 μM, the compounds of the invention exhibitedselective inhibition of PI3K or dual inhibition of Erk (MAPK1/2) and ofPI3K (see Table 3), which is indicated by inhibition of the phospho-bandintensity of the downstream substrates Rsk1 and Akt.

TABLE 3 Inhibition of cellular substrate phosphorylation (at 50 μM)Compound PI3K →pAkt Erk →pRsk 5 100% 0% 46  40% 100%  50 100% 0% 54 100%90%  55  90% 0% 56 100% 0%

Especially, pyridopyrazines such as compound 5 show total inhibition ofcellular phospho-Akt at compound concentrations<50 μM. The Raf-Mek-Erkpathway is not affected by these derivatives, as phospho-Rsk is notinhibited.

Also, pyridopyrazines, substituted by —NH-heteroaryl at the pyrazinering (for example, compounds 50, 55 and 56), exhibit cellular PI3Kselectivity, as they do not block the Raf-Mek-Erk pathway or showinhibition of phospho-Rsk respectively. Pyridopyrazines, substituted byheteroaryl at the pyrazine ring (for example, compounds 46 and 54)exhibit a dual mode of kinase inhibition, as they inhibit both, thePI3K-Akt and the Raf-Mek-Erk-Rsk pathways.

Abbreviations

-   Akt from: murine Akt8 retrovirus or protein kinase B (PKB)-   Ask1 apoptosis signal-regulating kinase-   ATR ataxia-telangiectasia and Rad3-related-   ATM ataxia-telangiectasia mutated-   Bag1 Bcl-2 associated athanogene-1-   Bcl-2 B-cell leukaemia/lymhoma-2 gene-   DNA-PK DNA-dependent protein kinase-   Erk extracellular signal-regulated kinase-   Flt-3 fms like tyrosine kinase 3-   GSK-3 glycogen synthase kinase-3-   hSMG-1 human orthologue of product of seven nematode gene-1-   JAK-3 Janus kinase 3-   JNK c-jun N-terminal kinase-   MAPK mitogen activated protein kinase-   Mek MAP or Erk kinase-   mTOR mammalian target of rapamycin-   PDGFR platelet derived growth factor receptor-   PI3K phosphoinositol 3-kinase-   PIKK phosphoinositol 3-kinase related kinase-   PIP₂ phosphatidylinositol biphosphate-   PIP₃ phosphatidylinositol triphosphate-   PtdIns phosphatidylinositol-   Raf rapid accelerated fibrosarcoma-   Ras rat sarcoma-   RTK receptor tyrosine kinase-   SAPK stress-activated protein kinase-   Ser serine-   Syk spleen tyrosine kinase-   Thr threonine-   Tyr tyrosine-   VEGFR vascular endothelial growth factor receptor

1-46. (canceled)
 47. A pyrido[2,3-b]pyrazine compound according toformula (Ia)

wherein: R1 is thiourea substituted with alkyl or cycloalkyl; R2 and R5are hydrogen; R3 and R4 are different and are hydrogen or heteroaryl,wherein heteroaryl is substitute with alkyl or cycloalkyl.
 48. Thepyrido[2,3-b]pyrazine compound of claim 47, which is1-ethyl-3-[3-(1-methyl-1H-pyrazol-4-yl)-pyrido[2,3-b]pyrazine-6-yl]thiourea.49. A composition comprising at least one compound according to claim47; and a pharmaceutically acceptable carrier and/or pharmaceuticallyacceptable auxilary.
 50. The composition according to claim 49, whereinthe at least one compound is present in a unit dose of from 0.001 mg to100 mg per kg of body weight of a patient.
 51. A composition comprisingthe compound according to claim 48; and a pharmaceutically acceptablecarrier and/or pharmaceutically acceptable auxilary.
 52. The compositionaccording to claim 51, wherein the compound is present in a unit dose offrom 0.001 mg to 100 mg per kg of body weight of a patient.
 53. Thepyrido[2,3-b]pyrazine compound according to claim 47, which is astereoisomer, a geometric isomer, or a tautomer.
 54. A compositioncomprising the pyrido[2,3-b]pyrazine compound according to claim 53; anda pharmaceutically acceptable carrier and/or pharmaceutically acceptableauxilary.
 55. The composition according to claim 54, wherein thecompound is present in a unit dose of from 0.001 mg to 100 mg per kg ofbody weight of a patient.